CAZypedia - User contributions [en-ca]

User:Eva Madland

2021-09-21T11:50:11Z

Eva Madland:

[[Image:Cazypedia_EM.jpg|200px|right]]

Eva Madland has a M.Sc. in organic chemistry from the Norwegian University of Science and Technology (Trondheim, Norway), where she worked on isolation, separation and structural elucidation of natural products from plants. In 2020 she completed her PhD in Biotechnology at the Norwegian University of Science and Technology (Trondheim, Norway) under the supervision by Professor [[User:Finn_Aachmann|Finn Lillelund Aachmann]] (NTNU, Norway) and Professor Morten Sørlie (NMBU, Norway) in the [https://folk.ntnu.no/aachmann/ Biopolymer NMR group]. The work focused on studying interactions between carbohydrate-binding modules and carbohydrates using NMR spectroscopy. She is currently a postdoc in the group of Associate professor [https://mbg.au.dk/forskning/forskningsomraader/plantemolekylaerbiologi/kasper-roejkjaer-andersen/ Kasper R. Andersen] (Aarhus University, Denmark) where she is working on structure and function relations of receptor-mediated signalling in plant-microbe interactions.

She has worked on the following CBMs:

* [[CBM5]] from ''Cellvibrio japonicus'' <cite>Madland2021</cite>
* [[CBM14]] from human chitotriosidase <cite>Madland2019</cite>
* [[CBM73]] from ''Cellvibrio japonicus'' <cite>Madland2021</cite>
* [[CBM86]] from ''Roseburia intestinalis'' L1-82 <cite>Madland2018,Leth2020</cite>

----

<biblio>
#Madland2018 pmid=30244308

#Leth2020 pmid=31693302

#Madland2019 pmid=31891077
#Madland2021 pmid=34411561

</biblio>


[[Category:Contributors|Madland,Eva]]

User:Eva Madland

2021-06-04T11:23:50Z

Eva Madland:

[[Image:Cazypedia_EM.jpg|200px|right]]

Eva Madland has a M.Sc. in organic chemistry from the Norwegian University of Science and Technology (Trondheim, Norway), where she worked on isolation, separation and structural elucidation of natural products from plants. In 2020 she completed her PhD in Biotechnology at the Norwegian University of Science and Technology (Trondheim, Norway) under the supervision by Professor [[User:Finn_Aachmann|Finn Lillelund Aachmann]] (NTNU, Norway) and Professor Morten Sørlie (NMBU, Norway) in the [https://folk.ntnu.no/aachmann/ Biopolymer NMR group]. The work focused on studying interactions between carbohydrate-binding modules and carbohydrates using NMR spectroscopy. She is currently a postdoc in the group of Associate professor [https://mbg.au.dk/forskning/forskningsomraader/plantemolekylaerbiologi/kasper-roejkjaer-andersen/ Kasper R. Andersen] (Aarhus University, Denmark) where she is working on structure and function relations of receptor-mediated signalling in plant-microbe interactions.

She has worked on the following CBMs:
* [[CBM14]] from human chitotriosidase <cite>Madland2019</cite>
* [[CBM86]] from ''Roseburia intestinalis'' L1-82 <cite>Madland2018,Leth2020</cite>

----

<biblio>
#Madland2018 pmid=30244308

#Leth2020 pmid=31693302

#Madland2019 pmid=31891077
</biblio>


[[Category:Contributors|Madland,Eva]]

User:Eva Madland

2021-06-03T07:34:50Z

Eva Madland:

Carbohydrate Binding Module Family 14

2020-12-02T13:19:41Z

Eva Madland:

{{UnderConstruction}}
* [[Author]]: ^^^Eva Madland^^^
* [[Responsible Curator]]: ^^^Elizabeth Ficko-Blean^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBMnn.html
|}
</div>


== Ligand specificities ==
Family 14 CBMs are modules composed of approximately 70 residues. These modules have been reported to be associated with chitinases <cite>Fadel2016</cite> and as chitin-binding lectins e.g. effector proteins from the tomato pathogens ''Pseudoercospora fuligena'' or ''Cladosporium fulvum'' <cite>Kohler2016 Hurlburt2018</cite>, as an antimicrobial protein (tachycitin) from horseshoe crab (''Tachypleus tridentatus'') hemocytes <cite>Kawabata1996</cite> and in peritrophic matrix proteins from the malaria vector ''Anopheles gambia'' <cite>Shen1998</cite>. Members of CBM14 have been shown to bind chitin <cite>Shen1998 Vandevenne2011 Madland2019</cite> and chitooligomers <cite>Crasson2016 Hurlburt2018</cite>; binding to 50 % acetylated hyaluronan has also been demonstrated <cite>Crasson2016</cite>.

The ligand binding affinities have been quantified for two CBM14 members. The interaction between a CBM14 from human chitotriosidase-1 (CHIT1, characterized as a glycoside hydrolase family 18 ([[GH18]])) and (GlcNAc)3 has been investigated. The CBM14 displayed a relatively weak interaction of KD 9.9 ± 0.8 mM using NMR titration experiments <cite>Crasson2016</cite> and KD 3.1 ± 0.2 mM using isothermal titration calorimetry (ITC) <cite>Madland2019</cite>.

Interaction studies have also been performed for a CBM14 from the fungal tomato pathogen ''C. fulvum'' and (GlcNAc)6. Here, the binding properties were measured using ITC yielding a KD of 6.7 ± 1.5 µM <cite>Hurlburt2018</cite>.

== Structural Features ==
[[File:Fig1-cbm14.png|thumb|300px|right|'''Figure 1 Example of CBM14 structures.''' A) ''Hs''CBM14 (PDB ID: [{{PDBlink}}6SO0 6SO0]) cartoon representation. Residues involved in binding (Trp465 and Asn466) are highlighted in cyan, Leu454 in purple, the two aromatic residues (Phe437 and Phe456) forming a hydrophobic core in white and disulfide briges in orange. B) Surface representation of ''Hs''CBM14. C) ''Cf''CBM14 (PDB ID: [{{PDBlink}}6BN0 6BN0]) cartoon representation. Residues involved in binding (Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103) are highlighted in cyan, the two aromatic residues (Tyr76 and Trp92) forming the hydrophobic core in white, disulfide briges in orange and (GlcNAc)6 in blue. D) Surface representation of ''Cf''CBM14.]]

CBM14 members have a hevein-like fold made up by a central β-sheet (three anti-parallel β-strands) linked to a small β-sheet (two anti-parallel β-strands) by two aromatic residues. The CBM14 members from tomato pathogens also have an N-terminal α-helix and an extended loop connecting -strands 2 and 3, as well as a C-terminal helical turn <cite>Kohler2016 Hurlburt2018</cite>. The latter is also present in tachycitin <cite>Suetake2000</cite>. In addtion, the CBM14 structures have been reported to contain 3-4 disulfide bridges which also serve as a stabilizing effect on this unique fold <cite>Suetake2000 Fadel2016 Hurlburt2018</cite>.
With the hevein-like fold and lectin-like properties, members of the CBM14 family are characterized as [[Carbohydrate-binding_modules#Types|type C]] CBMs <cite>Boraston2004</cite>. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (''Homo sapiens'' CBM14, ''Hs''CBM14). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of the module <cite>Crasson2016</cite> (Figure 1A). These residues create a platform-like binding surface (Figure 1B) commonly seen in [[Carbohydrate-binding_modules#Types|type A]] CBMs and could be the reason for why ''Hs''CBM14 is also able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) has been reported to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465 <cite>Madland2019</cite>. Binding between ''Hs''CBM14 and chitotriose is likely to occur through CH-π stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end <cite>Madland2019</cite>.

CBM14 from the tomato pathogen ''C. fulvum'' (''Cf''CBM14) was the first of these modules to be co-crystallized with (GlcNAc)6 (PDB ID: [{{PDBlink}}6BN0 6BN0])<cite>Hurlburt2018</cite>. Although the fold of ''Cf''CBM14 is the same as ''Hs''CBM14 (PDB ID: [{{PDBlink}}5HBF 5HBF] and [{{PDBlink}}6SO0 6SO0]) and other [http://www.cazy.org/CBM14_structure.html structurally characterized CBM14 members], the residues responsible for binding differ. Binding of (GlcNAc)6 is mediated by Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103 positioned along a shallow trench in the longitudinal axis of ''Cf''CBM14 (Figure 1C and D). Mutational studies showed that binding to (GlcNAc)6 was abolished by mutation of Trp100 and Asp102. The main interaction is reported to be a CH-π stacking between Trp100 and GlcNAc-5 aided by Met51 and Pro53 which are both in van der Waal distances to GlcNAc-1 and GlcNAc-3, respectively <cite>Hurlburt2018</cite>. Although equivalents to Trp100, Asp102 and Tyr103 have been reported to be important for chitin-binding in CBM14 from tomato pathogen ''P. fuligena'' (''Pf''CBM14) (equivalent residues: Trp94, Asp96 and Tyr97) <cite>Kohler2016</cite>, the extensive hydrogen bond network could point to a different binding mechanism for ''Cf''CBM14 that is more reminiscent of a [[Carbohydrate-binding_modules#Types|type B]] CBM.
== Functionalities ==
Several members of CBM14 are often encountered as chitin-binding lectins <cite>Kawabata1996 Burg2004 Suetake2000 Kohler2016 Hurlburt2018</cite>, while the members present in modular chitinases play a key role in targeting substrate <cite>Renkema1997 Tjoelker2000 Fadel2016</cite>. The most common associated modules are chitinases, e.g. [[GH18]] from human chitotriosidase structurally determined together with ''Hs''CBM14 (PDB ID: [{{PDBlink}}5HBF 5HBF])<cite>Fadel2016</cite>.

Although some of the structural features described above differ between the CBM14 lectins and ''Hs''CBM14, the common denominator is the involvement of these modules in immune responses <cite>Burg2006 Joosten1997 Fadel2016</cite>. CHIT1 is produced by macrophages and neutrophils <cite>Hollak1994, Kzhyshkowska2007</cite> and is utilized by the innate immune response to combat chitin-containing pathogens <cite>Gordon-Thomson2009</cite>. A different response is found in the tomato pathogen ''C. fulvum''; here, the effector protein utilizes CBM14's ability to bind chitin in the fungal cell wall enabling protection from hydrolysis by plant-derived chitinases during infection <cite>Joosten1997 Burg2006</cite>.
== Family Firsts ==
;First Identified: CBM14 was first identified as an antimicrobial protein with chitin-binding ability in the hemocyte of horseshoe crab (''T. tridentatus'') and called tachycitin <cite>Kawabata1996</cite>.
;First Structural Characterization: The first three-dimensional structure was determined by NMR spectroscopy for the CBM14 module tachycitin (PDB ID: [{{PDBlink}}1DQC 1DQC]) <cite>Suetake2000</cite>. The structure of the first carbohydrate-active enzyme associated CBM14 was determined by X-ray crystallography for the CBM14 of human chitotriosidase (PDB ID: [{{PDBlink}}5HBF 5HBF]) <cite>Fadel2016</cite>.

== References ==
<biblio>
#Fadel2016 pmid=27111557
#Kohler2016 pmid=27401545
#Hurlburt2018 pmid=30148881
#Kawabata1996 pmid=9010778
#Shen1998 pmid=9651363
#Vandevenne2011 pmid=21674664
#Madland2019 pmid=31891077
#Crasson2016 pmid=28584264
#Suetake2000 pmid=10770921
#Boraston2004 pmid=15214846
#Burg2004 pmid=14769793

#Renkema1997 pmid=9118991

#Tjoelker2000 pmid=10617646
#Hollak1994 pmid=8132768
#Kzhyshkowska2007 pmid=19662198
#Gordon-Thomson2009 pmid=19169854
#Joosten1997 pmid=9090881
#Burg2006 pmid=17153926
</biblio>

[[Category:Carbohydrate Binding Module Families|CBM014]]

Carbohydrate Binding Module Family 14

2020-12-02T12:24:29Z

Eva Madland:

{{UnderConstruction}}
* [[Author]]: ^^^Eva Madland^^^
* [[Responsible Curator]]: ^^^Elizabeth Ficko-Blean^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBMnn.html
|}
</div>


== Ligand specificities ==
Family 14 CBMs are modules composed of approximately 70 residues. These modules have been reported to be associated with chitinases <cite>Fadel2016</cite> and as chitin-binding lectins e.g. effector proteins from the tomato pathogens ''Pseudoercospora fuligena'' or ''Cladosporium fulvum'' <cite>Kohler2016 Hurlburt2018</cite>, as an antimicrobial protein (tachycitin) from horseshoe crab hemocytes <cite>Kawabata1996</cite> and in peritrophic matrix proteins from the malaria vector ''Anopheles gambia'' <cite>Shen1998</cite>. Members of CBM14 have been shown to bind chitin <cite>Shen1998 Vandevenne2011 Madland2019</cite> and chitooligomers <cite>Crasson2016 Hurlburt2018</cite>; binding to 50 % acetylated hyaluronan has also been demonstrated <cite>Crasson2016</cite>.

The ligand binding affinities have been quantified for two CBM14 members. The interaction between a CBM14 from human chitotriosidase-1 (CHIT1, characterized as a glycoside hydrolase family 18 ([[GH18]])) and (GlcNAc)3 has been investigated. The CBM14 displayed a relatively weak interaction of KD 9.9 ± 0.8 mM using NMR titration experiments <cite>Crasson2016</cite> and KD 3.1 ± 0.2 mM using isothermal titration calorimetry (ITC) <cite>Madland2019</cite>.

Interaction studies have also been performed for a CBM14 from the fungal tomato pathogen ''C. fulvum'' and (GlcNAc)6. Here, the binding properties were measured using ITC yielding a KD of 6.7 ± 1.5 µM <cite>Hurlburt2018</cite>.

== Structural Features ==
[[File:Fig1-cbm14.png|thumb|300px|right|'''Figure 1 Example of CBM14 structures.''' A) ''Hs''CBM14 (PDB ID: [{{PDBlink}}6SO0 6SO0]) cartoon representation. Residues involved in binding (Trp465 and Asn466) are highlighted in cyan, Leu454 in purple, the two aromatic residues (Phe437 and Phe456) forming a hydrophobic core in white and disulfide briges in orange. B) Surface representation of ''Hs''CBM14. C) ''Cf''CBM14 (PDB ID: [{{PDBlink}}6BN0 6BN0]) cartoon representation. Residues involved in binding (Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103) are highlighted in cyan, the two aromatic residues (Tyr76 and Trp92) forming the hydrophobic core in white, disulfide briges in orange and (GlcNAc)6 in blue. D) Surface representation of ''Cf''CBM14.]]

CBM14 members have a hevein-like fold made up by a central β-sheet (three anti-parallel β-strands) linked to a small β-sheet (two anti-parallel β-strands) by two aromatic residues. The CBM14 members from tomato pathogens also have an N-terminal α-helix and an extended loop connecting -strands 2 and 3, as well as a C-terminal helical turn <cite>Kohler2016 Hurlburt2018</cite>. The latter is also present in tachycitin <cite>Suetake2000</cite>. In addtion, the CBM14 structures have been reported to contain 3-4 disulfide bridges which also serve as a stabilizing effect on this unique fold <cite>Suetake2000 Fadel2016 Hurlburt2018</cite>.
With the hevein-like fold and lectin-like properties, members of the CBM14 family are characterized as [[Carbohydrate-binding_modules#Types|type C]] CBMs <cite>Boraston2004</cite>. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (''Homo sapiens'' CBM14, ''Hs''CBM14). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of the module <cite>Crasson2016</cite> (Figure 1A). These residues create a platform-like binding surface (Figure 1B) commonly seen in [[Carbohydrate-binding_modules#Types|type A]] CBMs and could be the reason for why ''Hs''CBM14 is also able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) has been reported to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465 <cite>Madland2019</cite>. Binding between ''Hs''CBM14 and chitotriose is likely to occur through CH-π stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end <cite>Madland2019</cite>.

CBM14 from the tomato pathogen ''C. fulvum'' (''Cf''CBM14) was the first of these modules to be co-crystallized with (GlcNAc)6 (PDB ID: [{{PDBlink}}6BN0 6BN0])<cite>Hurlburt2018</cite>. Although the fold of ''Cf''CBM14 is the same as ''Hs''CBM14 (PDB ID: [{{PDBlink}}5HBF 5HBF] and [{{PDBlink}}6SO0 6SO0]) and other [http://www.cazy.org/CBM14_structure.html structurally characterized CBM14 members], the residues responsible for binding differ. Binding of (GlcNAc)6 is mediated by Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103 positioned along a shallow trench in the longitudinal axis of ''Cf''CBM14 (Figure 1C and D). Mutational studies showed that binding to (GlcNAc)6 was abolished by mutation of Trp100 and Asp102. The main interaction is reported to be a CH-π stacking between Trp100 and GlcNAc-5 aided by Met51 and Pro53 which are both in van der Waal distances to GlcNAc-1 and GlcNAc-3, respectively <cite>Hurlburt2018</cite>. Although equivalents to Trp100, Asp102 and Tyr103 have been reported to be important for chitin-binding in CBM14 from tomato pathogen ''P. fuligena'' (''Pf''CBM14) (equivalent residues: Trp94, Asp96 and Tyr97) <cite>Kohler2016</cite>, the extensive hydrogen bond network could point to a different binding mechanism for ''Cf''CBM14 that is more reminiscent of a [[Carbohydrate-binding_modules#Types|type B]] CBM.
== Functionalities ==
Several members of CBM14 are often encountered as chitin-binding lectins <cite>Kawabata1996 Burg2004 Suetake2000 Kohler2016 Hurlburt2018</cite>, while the members present in modular chitinases play a key role in targeting substrate <cite>Renkema1997 Tjoelker2000 Fadel2016</cite>. The most common associated modules are chitinases, e.g. [[GH18]] from human chitotriosidase structurally determined together with ''Hs''CBM14 (PDB ID: [{{PDBlink}}5HBF 5HBF])<cite>Fadel2016</cite>.

Although some of the structural features described above differ between the CBM14 lectins and ''Hs''CBM14, the common denominator is the involvement of these modules in immune responses <cite>Burg2006 Joosten1997 Fadel2016</cite>. CHIT1 is produced by macrophages and neutrophils <cite>Hollak1994, Kzhyshkowska2007</cite> and is utilized by the innate immune response to combat chitin-containing pathogens <cite>Gordon-Thomson2009</cite>. A different response is found in the tomato pathogen ''C. fulvum''; here, the effector protein utilizes CBM14's ability to bind chitin in the fungal cell wall enabling protection from hydrolysis by plant-derived chitinases during infection <cite>Joosten1997 Burg2006</cite>.
== Family Firsts ==
;First Identified: CBM14 was first identified as an antimicrobial protein with chitin-binding ability in the hemocyte of horseshoe crab (''Tachypleus tridentatus'') and called tachycitin <cite>Kawabata1996</cite>.
;First Structural Characterization: The first three-dimensional structure was determined by NMR spectroscopy for the CBM14 module tachycitin (PDB ID: [{{PDBlink}}1DQC 1DQC]) <cite>Suetake2000</cite>. The structure of the first carbohydrate-active enzyme associated CBM14 was determined by X-ray crystallography for the CBM14 of human chitotriosidase (PDB ID: [{{PDBlink}}5HBF 5HBF]) <cite>Fadel2016</cite>.

== References ==
<biblio>
#Fadel2016 pmid=27111557
#Kohler2016 pmid=27401545
#Hurlburt2018 pmid=30148881
#Kawabata1996 pmid=9010778
#Shen1998 pmid=9651363
#Vandevenne2011 pmid=21674664
#Madland2019 pmid=31891077
#Crasson2016 pmid=28584264
#Suetake2000 pmid=10770921
#Boraston2004 pmid=15214846
#Burg2004 pmid=14769793

#Renkema1997 pmid=9118991

#Tjoelker2000 pmid=10617646
#Hollak1994 pmid=8132768
#Kzhyshkowska2007 pmid=19662198
#Gordon-Thomson2009 pmid=19169854
#Joosten1997 pmid=9090881
#Burg2006 pmid=17153926
</biblio>

[[Category:Carbohydrate Binding Module Families|CBM014]]

Carbohydrate Binding Module Family 14

2020-12-02T10:53:32Z

Eva Madland:

{{UnderConstruction}}
* [[Author]]: ^^^Eva Madland^^^
* [[Responsible Curator]]: ^^^Elizabeth Ficko-Blean^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBMnn.html
|}
</div>


== Ligand specificities ==
Family 14 CBMs are modules composed of approximately 70 residues. These modules have been reported to be associated with chitinases <cite>Fadel2016</cite> and as chitin-binding lectins or lectin-like proteins e.g. effector proteins from the tomato pathogens ''Pseudoercospora fuligena'' or ''Cladosporium fulvum'' <cite>Kohler2016 Hurlburt2018</cite>, as an antimicrobial lectin-like protein (tachycitin) from horseshoe crab hemocytes <cite>Kawabata1996</cite> and in peritrophic matrix proteins from the malaria vector ''Anopheles gambia'' <cite>Shen1998</cite>. Members of CBM14 have been shown to bind chitin <cite>Shen1998 Vandevenne2011 Madland2019</cite> and chitooligomers <cite>Crasson2016 Hurlburt2018</cite>; binding to 50 % acetylated hyaluronan has also been demonstrated <cite>Crasson2016</cite>.

The ligand binding affinities have been quantified for two CBM14 members. The interaction between a CBM14 from human chitotriosidase-1 (CHIT1, characterized as a glycoside hydrolase family 18 ([[GH18]])) and (GlcNAc)3 has been investigated. The CBM14 displayed a relatively weak interaction of KD 9.9 ± 0.8 mM using NMR titration experiments <cite>Crasson2016</cite> and KD 3.1 ± 0.2 mM using isothermal titration calorimetry (ITC) <cite>Madland2019</cite>.

Interaction studies have also been performed for a CBM14 from the fungal tomato pathogen ''C. fulvum'' and (GlcNAc)6. Here, the binding properties were measured using ITC yielding a KD of 6.7 ± 1.5 µM <cite>Hurlburt2018</cite>.

== Structural Features ==
[[File:Fig1-cbm14.png|thumb|300px|right|'''Figure 1 Example of CBM14 structures.''' A) ''Hs''CBM14 (PDB ID: [{{PDBlink}}6SO0 6SO0]) cartoon representation. Residues involved in binding (Trp465 and Asn466) are highlighted in cyan, Leu454 in purple, the two aromatic residues (Phe437 and Phe456) forming a hydrophobic core in white and disulfide briges in orange. B) Surface representation of ''Hs''CBM14. C) ''Cf''CBM14 (PDB ID: [{{PDBlink}}6BN0 6BN0]) cartoon representation. Residues involved in binding (Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103) are highlighted in cyan, the two aromatic residues (Tyr76 and Trp92) forming the hydrophobic core in white, disulfide briges in orange and (GlcNAc)6 in blue. D) Surface representation of ''Cf''CBM14.]]

CBM14 members have a hevein-like fold made up by a central β-sheet (three anti-parallel β-strands) linked to a small β-sheet (two anti-parallel β-strands) by two aromatic residues. The CBM14 members from tomato pathogens also have an N-terminal α-helix and an extended loop connecting -strands 2 and 3, as well as a C-terminal helical turn <cite>Kohler2016 Hurlburt2018</cite>. The latter is also present in tachycitin <cite>Suetake2000</cite>. In addtion, the CBM14 structures have been reported to contain 3-4 disulfide bridges which also serve as a stabilizing effect on this unique fold <cite>Suetake2000 Fadel2016 Hurlburt2018</cite>.
With the hevein-like fold and lectin-like properties, members of the CBM14 family are characterized as [[Carbohydrate-binding_modules#Types|type C]] CBMs <cite>Boraston2004</cite>. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (''Homo sapiens'' CBM14, ''Hs''CBM14). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of the module <cite>Crasson2016</cite> (Figure 1A). These residues create a platform-like binding surface (Figure 1B) commonly seen in [[Carbohydrate-binding_modules#Types|type A]] CBMs and could be the reason for why ''Hs''CBM14 is also able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) has been reported to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465 <cite>Madland2019</cite>. Binding between ''Hs''CBM14 and chitotriose is likely to occur through CH-π stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end <cite>Madland2019</cite>.

CBM14 from the tomato pathogen ''C. fulvum'' (''Cf''CBM14) was the first of these modules to be co-crystallized with (GlcNAc)6 (PDB ID: [{{PDBlink}}6BN0 6BN0])<cite>Hurlburt2018</cite>. Although the fold of ''Cf''CBM14 is the same as ''Hs''CBM14 (PDB ID: [{{PDBlink}}5HBF 5HBF] and [{{PDBlink}}6SO0 6SO0]) and other [http://www.cazy.org/CBM14_structure.html structurally characterized CBM14 members], the residues responsible for binding differ. Binding of (GlcNAc)6 is mediated by Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103 positioned along a shallow trench in the longitudinal axis of ''Cf''CBM14 (Figure 1C and D). Mutational studies showed that binding to (GlcNAc)6 was abolished by mutation of Trp100 and Asp102. The main interaction is reported to be a CH-π stacking between Trp100 and GlcNAc-5 aided by Met51 and Pro53 which are both in van der Waal distances to GlcNAc-1 and GlcNAc-3, respectively <cite>Hurlburt2018</cite>. Although equivalents to Trp100, Asp102 and Tyr103 have been reported to be important for chitin-binding in CBM14 from tomato pathogen ''P. fuligena'' (''Pf''CBM14) (equivalent residues: Trp94, Asp96 and Tyr97) <cite>Kohler2016</cite>, the extensive hydrogen bond network could point to a different binding mechanism for ''Cf''CBM14 that is more reminiscent of a [[Carbohydrate-binding_modules#Types|type B]] CBM.
== Functionalities ==
Several members of CBM14 are often encountered as chitin-binding lectins <cite>Kawabata1996 Burg2004 Suetake2000 Kohler2016 Hurlburt2018</cite>, while the members present in modular chitinases play a key role in targeting substrate <cite>Renkema1997 Tjoelker2000 Fadel2016</cite>. The most common associated modules are chitinases, e.g. [[GH18]] from human chitotriosidase structurally determined together with ''Hs''CBM14 (PDB ID: [{{PDBlink}}5HBF 5HBF])<cite>Fadel2016</cite>.

Although some of the structural features described above differ between the CBM14 lectins and ''Hs''CBM14, the common denominator is the involvement of these modules in immune responses <cite>Burg2006 Joosten1997 Fadel2016</cite>. CHIT1 is produced by macrophages and neutrophils <cite>Hollak1994, Kzhyshkowska2007</cite> and is utilized by the innate immune response to combat chitin-containing pathogens <cite>Gordon-Thomson2009</cite>. A different response is found in the tomato pathogen ''C. fulvum''; here, the effector protein utilizes CBM14's ability to bind chitin in the fungal cell wall enabling protection from hydrolysis by plant-derived chitinases during infection <cite>Joosten1997 Burg2006</cite>.
== Family Firsts ==
;First Identified: CBM14 was first identified as an antimicrobial lectin-like protein with chitin-binding ability in the hemocyte of horseshoe crab (''Tachypleus tridentatus'') and called tachycitin <cite>Kawabata1996</cite>.
;First Structural Characterization: The first three-dimensional structure was determined by NMR spectroscopy for the CBM14 module tachycitin (PDB ID: [{{PDBlink}}1DQC 1DQC]) <cite>Suetake2000</cite>. The structure of the first carbohydrate-active enzyme associated CBM14 was determined by X-ray crystallography for the CBM14 of human chitotriosidase (PDB ID: [{{PDBlink}}5HBF 5HBF]) <cite>Fadel2016</cite>.

== References ==
<biblio>
#Fadel2016 pmid=27111557
#Kohler2016 pmid=27401545
#Hurlburt2018 pmid=30148881
#Kawabata1996 pmid=9010778
#Shen1998 pmid=9651363
#Vandevenne2011 pmid=21674664
#Madland2019 pmid=31891077
#Crasson2016 pmid=28584264
#Suetake2000 pmid=10770921
#Boraston2004 pmid=15214846
#Burg2004 pmid=14769793

#Renkema1997 pmid=9118991

#Tjoelker2000 pmid=10617646
#Hollak1994 pmid=8132768
#Kzhyshkowska2007 pmid=19662198
#Gordon-Thomson2009 pmid=19169854
#Joosten1997 pmid=9090881
#Burg2006 pmid=17153926
</biblio>

[[Category:Carbohydrate Binding Module Families|CBM014]]

Carbohydrate Binding Module Family 14

2020-12-02T10:52:36Z

Eva Madland:

{{UnderConstruction}}
* [[Author]]: ^^^Eva Madland^^^
* [[Responsible Curator]]: ^^^Elizabeth Ficko-Blean^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBMnn.html
|}
</div>


== Ligand specificities ==
Family 14 CBMs are modules composed of approximately 70 residues. These modules have been reported to be associated with chitinases <cite>Fadel2016</cite> and as chitin-binding lectins or lectin-like proteins e.g. effector proteins from the tomato pathogens ''Pseudoercospora fuligena'' or ''Cladosporium fulvum'' <cite>Kohler2016 Hurlburt2018</cite>, as an antimicrobial lectin-like protein (tachycitin) from horseshoe crab hemocytes <cite>Kawabata1996</cite> and in peritrophic matrix proteins from the malaria vector ''Anopheles gambia'' <cite>Shen1998</cite>. Members of CBM14 have been shown to bind chitin <cite>Shen1998 Vandevenne2011 Madland2019</cite> and chitooligomers <cite>Crasson2016 Hurlburt2018</cite>; binding to 50 % acetylated hyaluronan has also been demonstrated <cite>Crasson2016</cite>.

The ligand binding affinities have been quantified for two CBM14 members. The interaction between a CBM14 from human chitotriosidase-1 (CHIT1, characterized as a glycoside hydrolase family 18 ([[GH18]])) and (GlcNAc)3 has been investigated. The CBM14 displayed a relatively weak interaction of KD 9.9 ± 0.8 mM using NMR titration experiments <cite>Crasson2016</cite> and KD 3.1 ± 0.2 mM using isothermal titration calorimetry (ITC) <cite>Madland2019</cite>.

Interaction studies have also been performed for a CBM14 from the fungal tomato pathogen ''C. fulvum'' and (GlcNAc)6. Here, the binding properties were measured using ITC yielding a KD of 6.7 ± 1.5 µM <cite>Hurlburt2018</cite>.

== Structural Features ==
[[File:Fig1-cbm14.png|thumb|300px|right|'''Figure 1 Example of CBM14 structures.''' A) ''Hs''CBM14 (PDB ID: [{{PDBlink}}6SO0 6SO0]) cartoon representation. Residues involved in binding (Trp465 and Asn466) are highlighted in cyan, Leu454 in purple, the two aromatic residues (Phe437 and Phe456) forming a hydrophobic core in white and disulfide briges in orange. B) Surface representation of ''Hs''CBM14. C) ''Cf''CBM14 (PDB ID: [{{PDBlink}}6BN0 6BN0]) cartoon representation. Residues involved in binding (Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103) are highlighted in cyan, the two aromatic residues (Tyr76 and Trp92) forming the hydrophobic core in white, disulfide briges in orange and (GlcNAc)6 in blue. D) Surface representation of ''Cf''CBM14.]]

CBM14 members have a hevein-like fold made up by a central β-sheet (three anti-parallel β-strands) linked to a small β-sheet (two anti-parallel β-strands) by two aromatic residues. The CBM14 members from tomato pathogens also have an N-terminal α-helix and an extended loop connecting -strands 2 and 3, as well as a C-terminal helical turn <cite>Kohler2016 Hurlburt2018</cite>. The latter is also present in tachycitin <cite>Suetake2000</cite>. In addtion, the CBM14 structures have been reported to contain 3-4 disulfide bridges which also serve as a stabilizing effect on this unique fold <cite>Suetake2000 Fadel2016 Hurlburt2018</cite>.
With the hevein-like fold and lectin-like properties, members of the CBM14 family are characterized as [[Carbohydrate-binding_modules#Types|type C]] CBMs <cite>Boraston2004</cite>. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (''Homo sapiens'' CBM14, ''Hs''CBM14). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of the module <cite>Crasson2016</cite> (Figure 1A). These residues create a platform-like binding surface (Figure 1B) commonly seen in [[Carbohydrate-binding_modules#Types|type A]] CBMs and could be the reason for why ''Hs''CBM14 is also able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) has been reported to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465 <cite>Madland2019</cite>. Binding between ''Hs''CBM14 and chitotriose is likely to occur through CH-π stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end <cite>Madland2019</cite>.

CBM14 from the tomato pathogen ''C. fulvum'' (''Cf''CBM14) was the first of these modules to be co-crystallized with (GlcNAc)6 (PDB ID: [{{PDBlink}}6BN0 6BN0])<cite>Hurlburt2018</cite>. Although the fold of ''Cf''CBM14 is the same as ''Hs''CBM14 (PDB ID: [{{PDBlink}}5HBF 5HBF] and [{{PDBlink}}6SO0 6SO0]) and other [http://www.cazy.org/CBM14_structure.html structurally characterized CBM14 members], the residues responsible for binding differ. Binding of (GlcNAc)6 is mediated by Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103 positioned along a shallow trench in the longitudinal axis of ''Cf''CBM14 (Figure 1C and D). Mutational studies showed that binding to (GlcNAc)6 was abolished by mutation of Trp100 and Asp102. The main interaction is reported to be a CH-π stacking between Trp100 and GlcNAc-5 aided by Met51 and Pro53 which are both in van der Waal distances to GlcNAc-1 and GlcNAc-3, respectively <cite>Hurlburt2018</cite>. Although equivalents to Trp100, Asp102 and Tyr103 have been reported to be important for chitin-binding in CBM14 from tomato pathogen ''P. fuligena'' (''Pf''CBM14) (equivalent residues: Trp94, Asp96 and Tyr97) <cite>Kohler2016</cite>, the extensive hydrogen bond network could point to a different binding mechanism for ''Cf''CBM14 that is more reminiscent of a [[Carbohydrate-binding_modules#Types|type B]] CBM.
== Functionalities ==
Several members of CBM14 are often encountered as chitin-binding lectins <cite>Kawabata1996 Burg2004 Suetake2000 Kohler2016 Hurlburt2018</cite>, while the members present in modular chitinases play a key role in targeting substrate <cite>Renkema1997 Tjoelker2000 Fadel2016</cite>. The most common associated modules are chitinases, e.g. [[GH18]] from human chitotriosidase structurally determined together with ''Hs''CBM14 (PDB ID: [{{PDBlink}}5HBF 5HBF])<cite>Fadel2016</cite>.

Although some of the structural features described above differ between the CBM14 lectins and ''Hs''CBM14, the common denominator is the involvement of these modules in immune responses. CHIT1 is produced by macrophages and neutrophils <cite>Hollak1994, Kzhyshkowska2007</cite> and is utilized by the innate immune response to combat chitin-containing pathogens <cite>Gordon-Thomson2009</cite>. A different response is found in the tomato pathogen ''C. fulvum''; here, the effector protein utilizes CBM14's ability to bind chitin in the fungal cell wall enabling protection from hydrolysis by plant-derived chitinases during infection <cite>Joosten1997 Burg2006</cite>.
== Family Firsts ==
;First Identified: CBM14 was first identified as an antimicrobial lectin-like protein with chitin-binding ability in the hemocyte of horseshoe crab (''Tachypleus tridentatus'') and called tachycitin <cite>Kawabata1996</cite>.
;First Structural Characterization: The first three-dimensional structure was determined by NMR spectroscopy for the CBM14 module tachycitin (PDB ID: [{{PDBlink}}1DQC 1DQC]) <cite>Suetake2000</cite>. The structure of the first carbohydrate-active enzyme associated CBM14 was determined by X-ray crystallography for the CBM14 of human chitotriosidase (PDB ID: [{{PDBlink}}5HBF 5HBF]) <cite>Fadel2016</cite>.

== References ==
<biblio>
#Fadel2016 pmid=27111557
#Kohler2016 pmid=27401545
#Hurlburt2018 pmid=30148881
#Kawabata1996 pmid=9010778
#Shen1998 pmid=9651363
#Vandevenne2011 pmid=21674664
#Madland2019 pmid=31891077
#Crasson2016 pmid=28584264
#Suetake2000 pmid=10770921
#Boraston2004 pmid=15214846
#Burg2004 pmid=14769793

#Renkema1997 pmid=9118991

#Tjoelker2000 pmid=10617646
#Hollak1994 pmid=8132768
#Kzhyshkowska2007 pmid=19662198
#Gordon-Thomson2009 pmid=19169854
#Joosten1997 pmid=9090881
#Burg2006 pmid=17153926
</biblio>

[[Category:Carbohydrate Binding Module Families|CBM014]]

Carbohydrate Binding Module Family 14

2020-12-02T10:44:59Z

Eva Madland:

{{UnderConstruction}}
* [[Author]]: ^^^Eva Madland^^^
* [[Responsible Curator]]: ^^^Elizabeth Ficko-Blean^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBMnn.html
|}
</div>


== Ligand specificities ==
Family 14 CBMs are modules composed of approximately 70 residues. These modules have been reported to be associated with chitinases <cite>Fadel2016</cite> and as chitin-binding lectins or lectin-like proteins e.g. effector proteins from the tomato pathogens ''Pseudoercospora fuligena'' or ''Cladosporium fulvum'' <cite>Kohler2016 Hurlburt2018</cite>, as an antimicrobial lectin-like protein (tachycitin) from horseshoe crab hemocytes <cite>Kawabata1996</cite> and in peritrophic matrix proteins from the malaria vector ''Anopheles gambia'' <cite>Shen1998</cite>. Members of CBM14 have been shown to bind chitin <cite>Shen1998 Vandevenne2011 Madland2019</cite> and chitooligomers <cite>Crasson2016 Hurlburt2018</cite>; binding to 50 % acetylated hyaluronan has also been demonstrated <cite>Crasson2016</cite>.

The ligand binding affinities have been quantified for two CBM14 members. The interaction between a CBM14 from human chitotriosidase-1 (CHIT1, characterized as a glycoside hydrolase family 18 ([[GH18]])) and (GlcNAc)3 has been investigated. The CBM14 displayed a relatively weak interaction of KD 9.9 ± 0.8 mM using NMR titration experiments <cite>Crasson2016</cite> and KD 3.1 ± 0.2 mM using isothermal titration calorimetry (ITC) <cite>Madland2019</cite>.

Interaction studies have also been performed for a CBM14 from the fungal tomato pathogen ''C. fulvum'' and (GlcNAc)6. Here, the binding properties were measured using ITC yielding a KD of 6.7 ± 1.5 µM <cite>Hurlburt2018</cite>.

== Structural Features ==
[[File:Fig1-cbm14.png|thumb|300px|right|'''Figure 1 Example of CBM14 structures.''' A) ''Hs''CBM14 (PDB ID: [{{PDBlink}}6SO0 6SO0]) cartoon representation. Residues involved in binding (Trp465 and Asn466) are highlighted in cyan, Leu454 in purple, the two aromatic residues (Phe437 and Phe456) forming a hydrophobic core in white and disulfide briges in orange. B) Surface representation of ''Hs''CBM14. C) ''Cf''CBM14 (PDB ID: [{{PDBlink}}6BN0 6BN0]) cartoon representation. Residues involved in binding (Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103) are highlighted in cyan, the two aromatic residues (Tyr76 and Trp92) forming the hydrophobic core in white, disulfide briges in orange and (GlcNAc)6 in blue. D) Surface representation of ''Cf''CBM14.]]

CBM14 members have a hevein-like fold made up by a central β-sheet (three anti-parallel β-strands) linked to a small β-sheet (two anti-parallel β-strands) by two aromatic residues. The CBM14 members from tomato pathogens also have an N-terminal α-helix and an extended loop connecting -strands 2 and 3, as well as a C-terminal helical turn <cite>Kohler2016 Hurlburt2018</cite>. The latter is also present in tachycitin <cite>Suetake2000</cite>. In addtion, the CBM14 structures have been reported to contain 3-4 disulfide bridges which also serve as a stabilizing effect on this unique fold <cite>Suetake2000 Fadel2016 Hurlburt2018</cite>.
With the hevein-like fold and lectin-like properties, members of the CBM14 family are characterized as [[Carbohydrate-binding_modules#Types|type C]] CBMs <cite>Boraston2004</cite>. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (''Homo sapiens'' CBM14, ''Hs''CBM14). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of the module <cite>Crasson2016</cite> (Figure 1A). These residues create a platform-like binding surface (Figure 1B) commonly seen in [[Carbohydrate-binding_modules#Types|type A]] CBMs and could be the reason for why ''Hs''CBM14 is also able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) has been reported to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465 <cite>Madland2019</cite>. Binding between ''Hs''CBM14 and chitotriose is likely to occur through CH-π stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end <cite>Madland2019</cite>.

CBM14 from the tomato pathogen ''C. fulvum'' (''Cf''CBM14) was the first of these modules to be co-crystallized with (GlcNAc)6 (PDB ID: [{{PDBlink}}6BN0 6BN0])<cite>Hurlburt2018</cite>. Although the fold of ''Cf''CBM14 is the same as ''Hs''CBM14 (PDB ID: [{{PDBlink}}5HBF 5HBF] and [{{PDBlink}}6SO0 6SO0]) and other [http://www.cazy.org/CBM14_structure.html structurally characterized CBM14 members], the residues responsible for binding differ. Binding of (GlcNAc)6 is mediated by Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103 positioned along a shallow trench in the longitudinal axis of ''Cf''CBM14 (Figure 1C and D). Mutational studies showed that binding to (GlcNAc)6 was abolished by mutation of Trp100 and Asp102. The main interaction is reported to be a CH-π stacking between Trp100 and GlcNAc-5 aided by Met51 and Pro53 which are both in van der Waal distances to GlcNAc-1 and GlcNAc-3, respectively <cite>Hurlburt2018</cite>. Although equivalents to Trp100, Asp102 and Tyr103 have been reported to be important for chitin-binding in CBM14 from tomato pathogen ''P. fuligena'' (''Pf''CBM14) (equivalent residues: Trp94, Asp96 and Tyr97) <cite>Kohler2016</cite>, the extensive hydrogen bond network could point to a different binding mechanism for ''Cf''CBM14 that is more reminiscent of a [[Carbohydrate-binding_modules#Types|type B]] CBM.
== Functionalities ==
Several members of CBM14 are often encountered as chitin-binding lectins <cite>Kawabata1996 Burg2004 Suetake2000 Kohler2016 Hurlburt2018</cite>, while the members present in modular chitinases play a key role in targeting substrate. The most common associated modules are chitinases, e.g. [[GH18]] from human chitotriosidase structurally determined together with ''Hs''CBM14 (PDB ID: [{{PDBlink}}5HBF 5HBF])<cite>Fadel2016</cite>.

Although some of the structural features described above differ between the CBM14 lectins and ''Hs''CBM14, the common denominator is the involvement of these modules in immune responses. CHIT1 is produced by macrophages and neutrophils <cite>Hollak1994, Kzhyshkowska2007</cite> and is utilized by the innate immune response to combat chitin-containing pathogens <cite>Gordon-Thomson2009</cite>. A similar response is found in the tomato pathogen ''C. fulvum''; here, the effector protein utilizes CBM14's ability to bind chitin in the fungal cell wall enabling protection from hydrolysis by plant-derived chitinases during infection <cite>Joosten1997 Burg2006</cite>.
== Family Firsts ==
;First Identified: CBM14 was first identified as an antimicrobial lectin-like protein with chitin-binding ability in the hemocyte of horseshoe crab (''Tachypleus tridentatus'') and called tachycitin <cite>Kawabata1996</cite>.
;First Structural Characterization: The first three-dimensional structure was determined by NMR spectroscopy for the CBM14 module tachycitin (PDB ID: [{{PDBlink}}1DQC 1DQC]) <cite>Suetake2000</cite>. The structure of the first carbohydrate-active enzyme associated CBM14 was determined by X-ray crystallography for the CBM14 of human chitotriosidase (PDB ID: [{{PDBlink}}5HBF 5HBF]) <cite>Fadel2016</cite>.

== References ==
<biblio>
#Fadel2016 pmid=27111557
#Kohler2016 pmid=27401545
#Hurlburt2018 pmid=30148881
#Kawabata1996 pmid=9010778
#Shen1998 pmid=9651363
#Vandevenne2011 pmid=21674664
#Madland2019 pmid=31891077
#Crasson2016 pmid=28584264
#Suetake2000 pmid=10770921
#Boraston2004 pmid=15214846
#Burg2004 pmid=14769793
#Hollak1994 pmid=8132768
#Kzhyshkowska2007 pmid=19662198
#Gordon-Thomson2009 pmid=19169854
#Joosten1997 pmid=9090881
#Burg2006 pmid=17153926
</biblio>

[[Category:Carbohydrate Binding Module Families|CBM014]]

Carbohydrate Binding Module Family 14

2020-12-02T10:42:03Z

Eva Madland:

{{UnderConstruction}}
* [[Author]]: ^^^Eva Madland^^^
* [[Responsible Curator]]: ^^^Elizabeth Ficko-Blean^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBMnn.html
|}
</div>


== Ligand specificities ==
Family 14 CBMs are modules composed of approximately 70 residues. These modules have been reported to be associated with chitinases <cite>Fadel2016</cite> and as chitin-binding lectins or lectin-like proteins e.g. effector proteins from the tomato pathogens ''Pseudoercospora fuligena'' or ''Cladosporium fulvum'' <cite>Kohler2016 Hurlburt2018</cite>, as an antimicrobial lectin-like protein (tachycitin) from horseshoe crab hemocytes <cite>Kawabata1996</cite> and in peritrophic matrix proteins from the malaria vector ''Anopheles gambia'' <cite>Shen1998</cite>. Members of CBM14 have been shown to bind chitin <cite>Shen1998 Vandevenne2011 Madland2019</cite> and chitooligomers <cite>Crasson2016 Hurlburt2018</cite>; binding to 50 % acetylated hyaluronan has also been demonstrated <cite>Crasson2016</cite>.

The ligand binding affinities have been quantified for two CBM14 members. The interaction between a CBM14 from human chitotriosidase-1 (CHIT1, characterized as a glycoside hydrolase family 18 ([[GH18]])) and (GlcNAc)3 has been investigated. The CBM14 displayed a relatively weak interaction of KD 9.9 ± 0.8 mM using NMR titration experiments <cite>Crasson2016</cite> and KD 3.1 ± 0.2 mM using isothermal titration calorimetry (ITC) <cite>Madland2019</cite>.

Interaction studies have also been performed for a CBM14 from the fungal tomato pathogen ''C. fulvum'' and (GlcNAc)6. Here, the binding properties were measured using ITC yielding a KD of 6.7 ± 1.5 µM <cite>Hurlburt2018</cite>.

== Structural Features ==
[[File:Fig1-cbm14.png|thumb|300px|right|'''Figure 1 Example of CBM14 structures.''' A) CBM14CHIT1 (PDB ID: [{{PDBlink}}6SO0 6SO0]) cartoon representation. Residues involved in binding (Trp465 and Asn466) are highlighted in cyan, Leu454 in purple, the two aromatic residues (Phe437 and Phe456) forming a hydrophobic core in white and disulfide briges in orange. B) Surface representation of CBM14CHIT1. C) ''Cf''CBM14 (PDB ID: [{{PDBlink}}6BN0 6BN0]) cartoon representation. Residues involved in binding (Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103) are highlighted in cyan, the two aromatic residues (Tyr76 and Trp92) forming the hydrophobic core in white, disulfide briges in orange and (GlcNAc)6 in blue. D) Surface representation of ''Cf''CBM14.]]

CBM14 members have a hevein-like fold made up by a central β-sheet (three anti-parallel β-strands) linked to a small β-sheet (two anti-parallel β-strands) by two aromatic residues. The CBM14 members from tomato pathogens also have an N-terminal α-helix and an extended loop connecting -strands 2 and 3, as well as a C-terminal helical turn <cite>Kohler2016 Hurlburt2018</cite>. The latter is also present in tachycitin <cite>Suetake2000</cite>. In addtion, the CBM14 structures have been reported to contain 3-4 disulfide bridges which also serve as a stabilizing effect on this unique fold <cite>Suetake2000 Fadel2016 Hurlburt2018</cite>.
With the hevein-like fold and lectin-like properties, members of the CBM14 family are characterized as [[Carbohydrate-binding_modules#Types|type C]] CBMs <cite>Boraston2004</cite>. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (''Homo sapiens'' CBM14, ''Hs''CBM14). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of the module <cite>Crasson2016</cite> (Figure 1A). These residues create a platform-like binding surface (Figure 1B) commonly seen in [[Carbohydrate-binding_modules#Types|type A]] CBMs and could be the reason for why ''Hs''CBM14 is also able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) has been reported to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465 <cite>Madland2019</cite>. Binding between ''Hs''CBM14 and chitotriose is likely to occur through CH-π stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end <cite>Madland2019</cite>.

CBM14 from the tomato pathogen ''C. fulvum'' (''Cf''CBM14) was the first of these modules to be co-crystallized with (GlcNAc)6 (PDB ID: [{{PDBlink}}6BN0 6BN0])<cite>Hurlburt2018</cite>. Although the fold of ''Cf''CBM14 is the same as ''Hs''CBM14 (PDB ID: [{{PDBlink}}5HBF 5HBF] and [{{PDBlink}}6SO0 6SO0]) and other [http://www.cazy.org/CBM14_structure.html structurally characterized CBM14 members], the residues responsible for binding differ. Binding of (GlcNAc)6 is mediated by Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103 positioned along a shallow trench in the longitudinal axis of ''Cf''CBM14 (Figure 1C and D). Mutational studies showed that binding to (GlcNAc)6 was abolished by mutation of Trp100 and Asp102. The main interaction is reported to be a CH-π stacking between Trp100 and GlcNAc-5 aided by Met51 and Pro53 which are both in van der Waal distances to GlcNAc-1 and GlcNAc-3, respectively <cite>Hurlburt2018</cite>. Although equivalents to Trp100, Asp102 and Tyr103 have been reported to be important for chitin-binding in CBM14 from tomato pathogen ''P. fuligena'' (''Pf''CBM14) (equivalent residues: Trp94, Asp96 and Tyr97) <cite>Kohler2016</cite>, the extensive hydrogen bond network could point to a different binding mechanism for ''Cf''CBM14 that is more reminiscent of a [[Carbohydrate-binding_modules#Types|type B]] CBM.
== Functionalities ==
Several members of CBM14 are often encountered as chitin-binding lectins <cite>Kawabata1996 Burg2004 Suetake2000 Kohler2016 Hurlburt2018</cite>, while the members present in modular chitinases play a key role in targeting substrate. The most common associated modules are chitinases, e.g. [[GH18]] from human chitotriosidase structurally determined together with ''Hs''CBM14 (PDB ID: [{{PDBlink}}5HBF 5HBF])<cite>Fadel2016</cite>.

Although some of the structural features described above differ between the CBM14 lectins and ''Hs''CBM14, the common denominator is the involvement of these modules in immune responses. CHIT1 is produced by macrophages and neutrophils <cite>Hollak1994, Kzhyshkowska2007</cite> and is utilized by the innate immune response to combat chitin-containing pathogens <cite>Gordon-Thomson2009</cite>. A similar response is found in the tomato pathogen ''C. fulvum''; here, the effector protein utilizes CBM14's ability to bind chitin in the fungal cell wall enabling protection from hydrolysis by plant-derived chitinases during infection <cite>Joosten1997 Burg2006</cite>.
== Family Firsts ==
;First Identified: CBM14 was first identified as an antimicrobial lectin-like protein with chitin-binding ability in the hemocyte of horseshoe crab (''Tachypleus tridentatus'') and called tachycitin <cite>Kawabata1996</cite>.
;First Structural Characterization: The first three-dimensional structure was determined by NMR spectroscopy for the CBM14 module tachycitin (PDB ID: [{{PDBlink}}1DQC 1DQC]) <cite>Suetake2000</cite>. The structure of the first carbohydrate-active enzyme associated CBM14 was determined by X-ray crystallography for the CBM14 of human chitotriosidase (PDB ID: [{{PDBlink}}5HBF 5HBF]) <cite>Fadel2016</cite>.

== References ==
<biblio>
#Fadel2016 pmid=27111557
#Kohler2016 pmid=27401545
#Hurlburt2018 pmid=30148881
#Kawabata1996 pmid=9010778
#Shen1998 pmid=9651363
#Vandevenne2011 pmid=21674664
#Madland2019 pmid=31891077
#Crasson2016 pmid=28584264
#Suetake2000 pmid=10770921
#Boraston2004 pmid=15214846

#Burg2004 pmid=14769793
#Hollak1994 pmid=8132768
#Kzhyshkowska2007 pmid=19662198
#Gordon-Thomson2009 pmid=19169854
#Joosten1997 pmid=9090881
#Burg2006 pmid=17153926
</biblio>

[[Category:Carbohydrate Binding Module Families|CBM014]]

Carbohydrate Binding Module Family 14

2020-11-30T09:00:28Z

Eva Madland:

{{UnderConstruction}}
* [[Author]]: ^^^Eva Madland^^^
* [[Responsible Curator]]: ^^^Elizabeth Ficko-Blean^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBMnn.html
|}
</div>


== Ligand specificities ==
Family 14 CBMs are modules composed of approximately 70 residues. These modules have been reported to be associated with chitinases <cite>Fadel2016</cite> and as chitin-binding lectins e.g. effector protein from the tomato pathogens ''Pseudoercospora fuligena'' or ''Cladosporium fulvum'' <cite>Kohler2016 Hurlburt2018</cite>, as an antimicrobial lectin-like protein (tachycitin) from horseshoe crab hemocytes <cite>Kawabata1996</cite> and in peritrophic matrix proteins from Malaria vector ''Anopheles gambia'' <cite>Shen1998</cite>. Members of CBM14 have been shown to bind chitin <cite>Shen1998 Vandevenne2011 Madland2019</cite> and chitooligomers <cite>Crasson2016 Hurlburt2018</cite>. Binding to 50 % acetylated hyaluronan has also been demonstrated <cite>Crasson2016</cite>.

The ligand binding affinities have been quantified for two CBM14 members. The interaction between a human chitotriosidase-1 (CHIT1, characterized as a glycoside hydrolase family 18 ([[GH18]])) CBM14 and (GlcNAc)3 have been investigated with NMR titration experiments and isothermal titration calorimetry (ITC) displaying a relatively weak interaction of Kd 9.9 ± 0.8 mM <cite>Crasson2016</cite> and Kd 3.1 ± 0.2 mM <cite>Madland2019</cite>, respectively.

Interaction studies have also been performed for CBM14 in the fungal tomato pathogen ''C. fulvum'' and (GlcNAc)6. Here, the binding properties were measured using ITC yielding a Kd of 6.7 ± 1.5 µM <cite>Hurlburt2018</cite>.

== Structural Features ==
[[File:Fig1-cbm14.png|thumb|300px|right|'''Figure 1 Example of CBM14 structures.''' A) CBM14CHIT1 (PDB ID: [{{PDBlink}}6SO0 6SO0]) cartoon representation. Residues involved in binding (Trp465 and Asn466) are highlighted in cyan, Leu454 in purple, the two aromatic residues (Phe437 and Phe456) forming a hydrophobic core in white and disulfide briges in orange. B) Surface representation of CBM14CHIT1. C) ''Cf''CBM14 (PDB ID: [{{PDBlink}}6BN0 6BN0]) cartoon representation. Residues involved in binding (Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103) are highlighted in cyan, the two aromatic residues (Tyr76 and Trp92) forming the hydrophobic core in white, disulfide briges in orange and (GlcNAc)6 in blue. D) Surface representation of ''Cf''CBM14.]]

The structures of CBM14 members have a hevein-like fold commonly made up by a central β-sheet (three anti-parallel β-strands) linked to a small β-sheet (two anti-parallel β-strands) by two aromatic residues. The CBM14 members from tomato pathogens also have an N-terminal α-helix and an extended loop connecting -strands 2 and 3, as well as a C-terminal helical turn <cite>Kohler2016 Hurlburt2018</cite>. The latter is also present in tachycitin <cite>Suetake2000</cite>. In addtion, the CBM14 structures have been reported to contain 3-4 disulfide bridges which also serve as a stabilizing effect on this unique fold <cite>Suetake2000 Fadel2016 Hurlburt2018</cite>.
With this hevein-like fold and lectin properties, CBM14 is characterized as a Type C CBM <cite>Boraston2004</cite>. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (CBM14CHIT1). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of this module <cite>Crasson2016</cite> (Figure 1A). These residues create a platform-like binding surface (Figure 1B) commonly seen in Type A CBMs and could be the reason for why CBM14CHIT1 also is able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) have been reported <cite>Madland2019</cite> to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465. Binding between CBM14CHIT1 and chitotriose is likely to occur through CH-π stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end <cite>Madland2019</cite>.

CBM14 from the tomato pathogen ''C. fulvum'' (''Cf''CBM14) was the first of these modules to be co-crystallized with (GlcNAc)6 (PDB ID: [{{PDBlink}}6BN0 6BN0])<cite>Hurlburt2018</cite>. Although the fold of ''Cf''CBM14 is the same as CBM14CHIT1 (PDB ID: [{{PDBlink}}5HBF 5HBF] and [{{PDBlink}}6SO0 6SO0]) and other [http://www.cazy.org/CBM14_structure.html structurally characterized CBM14 members], the residues responsible for binding differ. Binding of (GlcNAc)6 is mediated by Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103 positioned along a shallow trench in the longitudinal axis of ''Cf''CBM14 (Figure 1C and D). Mutational studies showed that binding to (GlcNAc)6 was abolished by mutation of Trp100 and Asp102. The main interaction is reported to be a CH-π stacking between Trp100 and GlcNAc-5 aided by Met51 and Pro53 which are both in van der Waal distances to GlcNAc-1 and GlcNAc-3, respectively <cite>Hurlburt2018</cite>. Although equivalents to Trp100, Asp102 and Tyr103 have been reported to be important for chitin-binding in CBM14 from tomato pathogen ''P. fuligena'' (''Pf''CBM14) (equivalent residues: Trp94, Asp96 and Tyr97) <cite>Kohler2016</cite>, the extensive hydrogen bond network could point to a different binding mechanism for ''Cf''CBM14 that is more reminiscent of a Type B CBM.
== Functionalities ==
Several members of CBM14 are often encountered as chitin-binding lectins <cite>Kawabata1996 Burg2004 Suetake2000 Kohler2016 Hurlburt2018</cite>, while the members present in modular chitinases play a key role in targeting substrate. The most common associated modules are chitinases, e.g. [[GH18]] from human chitotriosidase structurally determined together with CBM14CHIT1 (PDB ID: [{{PDBlink}}5HBF 5HBF])<cite>Fadel2016</cite>.

Although some of the structural features described above differ between the lectin-CBM14 and CBM14CHIT1, the common denominator is the involvement of these modules in immune responses. CHIT1 is produced by macrophages and neutrophils <cite>Hollak1994, Kzhyshkowska2007</cite> and is utilized by innate immune response to combat chitin-containing pathogens <cite>Gordon-Thomson2009</cite>. A similar response is found in the tomato pathogen ''C. fulvum''. Here, the effector protein utilizes CBM14's ability to bind chitin in the fungal cell wall enabling protection from hydrolysis by plant-derived chitinases during infection <cite>Joosten1997 Burg2006</cite>.
== Family Firsts ==
;First Identified
:CBM14 was first identified as an antimicrobial lectin-like protein with chitin binding ability in the hemocyte of horseshoe crab (''Tachypleus tridentatus'') and called tachycitin <cite>Kawabata1996</cite>.
;First Structural Characterization
:The first three-dimensional structure was determined by NMR spectroscopy for the CBM14 module tachycitin (PDB ID: [{{PDBlink}}1DQC 1DQC]) <cite>Suetake2000</cite>. The structure of the first carbohydrate-active enzyme associated CBM14 was determined by X-ray crystallography for the CBM14 of human chitotriosidase (PDB ID: [{{PDBlink}}5HBF 5HBF]) <cite>Fadel2016</cite>.

== References ==
<biblio>
#Fadel2016 pmid=27111557
#Kohler2016 pmid=27401545
#Hurlburt2018 pmid=30148881
#Kawabata1996 pmid=9010778
#Shen1998 pmid=9651363
#Vandevenne2011 pmid=21674664
#Madland2019 pmid=31891077
#Crasson2016 pmid=28584264
#Suetake2000 pmid=10770921
#Boraston2004 pmid=15214846

#Burg2004 pmid=14769793
#Hollak1994 pmid=8132768
#Kzhyshkowska2007 pmid=19662198
#Gordon-Thomson2009 pmid=19169854
#Joosten1997 pmid=9090881
#Burg2006 pmid=17153926
</biblio>

[[Category:Carbohydrate Binding Module Families|CBM014]]

Carbohydrate Binding Module Family 14

2020-11-27T15:01:31Z

Eva Madland:

{{UnderConstruction}}
* [[Author]]: ^^^Eva Madland^^^
* [[Responsible Curator]]: ^^^Elizabeth Ficko-Blean^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBMnn.html
|}
</div>


== Ligand specificities ==
Family 14 CBMs are modules composed of approximately 70 residues. These modules have been reported to be associated with chitinases <cite>Fadel2016</cite> and as chitin-binding lectins e.g. an effector protein from the tomato pathogen ''Pseudoercospora fuligena'' or ''Cladosporium fulvum'' <cite>Kohler2016 Hurlburt2018</cite>, as an antimicrobial lectin-like protein (tachycitin) from horseshoe crab hemocytes <cite>Kawabata1996</cite> and in peritrophic matrix proteins from Malaria vector ''Anopheles gambia'' <cite>Shen1998</cite>. Members of CBM14 have been shown to bind chitin <cite>Shen1998 Vandevenne2011 Madland2019</cite> and chitooligomers <cite>Crasson2016 Hurlburt2018</cite>. Binding to 50 % acetylated hyaluronan has also been demonstrated <cite>Crasson2016</cite>.

The ligand binding affinities have been quantified for two CBM14 members. The interaction between a human chitotriosidase-1 (CHIT1, characterized as a glycoside hydrolase family 18 ([[GH18]])) CBM14 and (GlcNAc)3 have been investigated with NMR titration experiments and isothermal titration calorimetry (ITC) displaying a relatively weak interaction of Kd 9.9 ± 0.8 mM <cite>Crasson2016</cite> and Kd 3.1 ± 0.2 mM <cite>Madland2019</cite>, respectively.

Interaction studies have also been performed for CBM14 in the fungal tomato pathogen ''C. fulvum'' and (GlcNAc)6. Here, the binding properties were measured using ITC yielding a Kd of 6.7 ± 1.5 µM <cite>Hurlburt2018</cite>.

== Structural Features ==
[[File:Fig1-cbm14.png|thumb|300px|right|'''Figure 1 Example of CBM14 structures.''' A) CBM14CHIT1 (PDB ID: [https://www.rcsb.org/structure/6SO0 6SO0]) cartoon representation. Residues involved in binding (Trp465 and Asn466) are highlighted in cyan, Leu454 in purple, the two aromatic residues (Phe437 and Phe456) forming a hydrophobic core in white and disulfide briges in orange. B) Surface representation of CBM14CHIT1. C) ''Cf''CBM14 (PDB ID: [https://www.rcsb.org/structure/6BN0 6BN0]) cartoon representation. Residues involved in binding (Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103) are highlighted in cyan, the two aromatic residues (Tyr76 and Trp92) forming the hydrophobic core in white, disulfide briges in orange and (GlcNAc)6 in blue. D) Surface representation of ''Cf''CBM14.]]

The structures of CBM14 members have a hevein-like fold commonly made up by a central β-sheet (three anti-parallel β-strands) linked to a small β-sheet (two anti-parallel β-strands) by two aromatic residues. The CBM14 members from tomato pathogens also have an N-terminal α-helix and an extended loop connecting -strands 2 and 3, as well as a C-terminal helical turn <cite>Kohler2016 Hurlburt2018</cite>. The latter is also present in tachycitin <cite>Suetake2000</cite>. In addtion, the CBM14 structures have been reported to contain 3-4 disulfide bridges which also serve as a stabilizing effect on this unique fold <cite>Suetake2000 Fadel2016 Hurlburt2018</cite>.
With this hevein-like fold and lectin properties, CBM14 is characterized as a Type C CBM <cite>Boraston2004</cite>. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (CBM14CHIT1). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of this module <cite>Crasson2016</cite> (Figure 1A). These residues create a platform-like binding surface (Figure 1B) commonly seen in Type A CBMs and could be the reason for why CBM14CHIT1 also is able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) have been reported <cite>Madland2019</cite> to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465. Binding between CBM14CHIT1 and chitotriose is likely to occur through CH-π stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end <cite>Madland2019</cite>.

CBM14 from the tomato pathogen ''C. fulvum'' (''Cf''CBM14) was the first of these modules to be co-crystallized with (GlcNAc)6 (PDB ID: [https://www.rcsb.org/structure/6BN0 6BN0])<cite>Hurlburt2018</cite>. Although the fold of ''Cf''CBM14 is the same as CBM14CHIT1 (PDB ID: [https://www.rcsb.org/structure/5HBF 5HBF] and [https://www.rcsb.org/structure/6SO0 6SO0]) and other [http://www.cazy.org/CBM14_structure.html structurally characterized CBM14 members], the residues responsible for binding differ. Binding of (GlcNAc)6 is mediated by Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103 positioned along a shallow trench in the longitudinal axis of ''Cf''CBM14 (Figure 1C and D). Mutational studies showed that binding to (GlcNAc)6 was abolished by mutation of Trp100 and Asp102. The main interaction is reported to be a CH-π stacking between Trp100 and GlcNAc-5 aided by Met51 and Pro53 which are both in van der Waal distances to GlcNAc-1 and GlcNAc-3, respectively <cite>Hurlburt2018</cite>. Although equivalents to Trp100, Asp102 and Tyr103 have been reported to be important for chitin-binding in CBM14 from tomato pathogen ''P. fuligena'' (''Pf''CBM14) (equivalent residues: Trp94, Asp96 and Tyr97) <cite>Kohler2016</cite>, the extensive hydrogen bond network could point to a different binding mechanism for ''Cf''CBM14 that is more reminiscent of a Type B CBM.
== Functionalities ==
Several members of CBM14 are often encountered as chitin-binding lectins <cite>Kawabata1996 Burg2004 Suetake2000 Kohler2016 Hurlburt2018</cite>, while the members present in modular chitinases play a key role in targeting substrate. The most common associated modules are chitinases, e.g. [[GH18]] from human chitotriosidase structurally determined together with CBM14CHIT1 (PDB ID: [https://www.rcsb.org/structure/5HBF 5HBF])<cite>Fadel2016</cite>.

Although some of the structural features described above differ between the lectin-CBM14 and CBM14CHIT1, the common denominator is the involvement of these modules in immune responses. CHIT1 is produced by macrophages and neutrophils <cite>Hollak1994, Kzhyshkowska2007</cite> and is utilized by innate immune response to combat chitin-containing pathogens <cite>Gordon-Thomson2009</cite>. A similar response is found in the tomato pathogen ''C. fulvum''. Here, the effector protein utilizes CBM14's ability to bind chitin in the fungal cell wall enabling protection from hydrolysis by plant-derived chitinases during infection <cite>Joosten1997 Burg2006</cite>.
== Family Firsts ==
;First Identified
:CBM14 was first identified as an antimicrobial lectin-like protein with chitin binding ability in the hemocyte of horseshoe crab (''Tachypleus tridentatus'') and called tachycitin <cite>Kawabata1996</cite>.
;First Structural Characterization
:The first three-dimensional structure was determined by NMR spectroscopy for the CBM14 module tachycitin (PDB ID: [https://www.rcsb.org/structure/1DQC 1DQC]) <cite>Suetake2000</cite>. The structure of the first carbohydrate-active enzyme associated CBM14 was determined by X-ray crystallography for the CBM14 of human chitotriosidase (PDB ID: [https://www.rcsb.org/structure/5HBF 5HBF]) <cite>Fadel2016</cite>.

== References ==
<biblio>
#Fadel2016 pmid=27111557
#Kohler2016 pmid=27401545
#Hurlburt2018 pmid=30148881
#Kawabata1996 pmid=9010778
#Shen1998 pmid=9651363
#Vandevenne2011 pmid=21674664
#Madland2019 pmid=31891077
#Crasson2016 pmid=28584264
#Suetake2000 pmid=10770921
#Boraston2004 pmid=15214846

#Burg2004 pmid=14769793
#Hollak1994 pmid=8132768
#Kzhyshkowska2007 pmid=19662198
#Gordon-Thomson2009 pmid=19169854
#Joosten1997 pmid=9090881
#Burg2006 pmid=17153926
</biblio>

[[Category:Carbohydrate Binding Module Families|CBM014]]

Carbohydrate Binding Module Family 14

2020-11-27T14:59:08Z

Eva Madland:

{{UnderConstruction}}
* [[Author]]: ^^^Eva Madland^^^
* [[Responsible Curator]]: ^^^Elizabeth Ficko-Blean^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBMnn.html
|}
</div>


== Ligand specificities ==
Family 14 CBMs are modules composed of approximately 70 residues. These modules have been reported to be associated with chitinases <cite>Fadel2016</cite> and as chitin-binding lectins e.g. an effector protein from the tomato pathogen ''Pseudoercospora fuligena'' or ''Cladosporium fulvum'' <cite>Kohler2016 Hurlburt2018</cite>, as an antimicrobial lectin-like protein (tachycitin) from horseshoe crab hemocytes <cite>Kawabata1996</cite> and in peritrophic matrix proteins from Malaria vector ''Anopheles gambia'' <cite>Shen1998</cite>. Members of CBM14 have been shown to bind chitin <cite>Shen1998 Vandevenne2011 Madland2019</cite> and chitooligomers <cite>Crasson2016 Hurlburt2018</cite>. Binding to 50 % acetylated hyaluronan has also been demonstrated <cite>Crasson2016</cite>.

The ligand binding affinities have been quantified for two CBM14 members. The interaction between a human chitotriosidase-1 (CHIT1, characterized as a glycoside hydrolase family 18 ([[GH18]])) CBM14 and (GlcNAc)3 have been investigated with NMR titration experiments and isothermal titration calorimetry (ITC) displaying a relatively weak interaction of Kd 9.9 ± 0.8 mM <cite>Crasson2016</cite> and Kd 3.1 ± 0.2 mM <cite>Madland2019</cite>, respectively.

Interaction studies have also been performed for CBM14 in the fungal tomato pathogen ''C. fulvum'' and (GlcNAc)6. Here, the binding properties were measured using ITC yielding a Kd of 6.7 ± 1.5 µM <cite>Hurlburt2018</cite>.

== Structural Features ==
[[File:Fig1-cbm14.png|thumb|300px|right|'''Figure 1 Example of CBM14 structures.''' A) CBM14CHIT1 (PDB ID: [https://www.rcsb.org/structure/6SO0 6SO0]) cartoon representation. Residues involved in binding (Trp465 and Asn466) are highlighted in cyan, Leu454 in purple, the two aromatic residues (Phe437 and Phe456) forming a hydrophobic core in white and disulfide briges in orange. B) Surface representation of CBM14CHIT1. C) ''Cf''CBM14 (PDB ID: [https://www.rcsb.org/structure/6BN0 6BN0]) cartoon representation. Residues involved in binding (Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103) are highlighted in cyan, the two aromatic residues (Tyr76 and Trp92) forming the hydrophobic core in white, disulfide briges in orange and (GlcNAc)6 in blue. D) Surface representation of ''Cf''CBM14.]]

The structures of CBM14 members have a hevein-like fold commonly made up by a central β-sheet (three anti-parallel β-strands) linked to a small β-sheet (two anti-parallel β-strands) by two aromatic residues. The CBM14 members from tomato pathogens also have an N-terminal α-helix and an extended loop connecting -strands 2 and 3, as well as a C-terminal helical turn <cite>Kohler2016 Hurlburt2018</cite>. The latter is also present in tachycitin <cite>Suetake2000</cite>. In addtion, the CBM14 structures have been reported to contain 3-4 disulfide bridges which also serve as a stabilizing effect on this unique fold <cite>Suetake2000 Fadel2016 Hurlburt2018</cite>.
With this hevein-like fold and lectin properties, CBM14 is characterized as a Type C CBM <cite>Boraston2004</cite>. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (CBM14CHIT1). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of this module <cite>Crasson2016</cite> (Figure 1A). These residues create a platform-like binding surface (Figure 1B) commonly seen in Type A CBMs and could be the reason for why CBM14CHIT1 also is able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) have been reported <cite>Madland2019</cite> to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465. Binding between CBM14CHIT1 and chitotriose is likely to occur through CH-π stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end <cite>Madland2019</cite>.

CBM14 from the tomato pathogen ''C. fulvum'' (''Cf''CBM14) was the first of these modules to be co-crystallized with (GlcNAc)6 (PDB ID: [https://www.rcsb.org/structure/6BN0 6BN0])<cite>Hurlburt2018</cite>. Although the fold of ''Cf''CBM14 is the same as CBM14CHIT1 and other [http://www.cazy.org/CBM14_structure.html structurally characterized CBM14 members], the residues responsible for binding differ. Binding of (GlcNAc)6 is mediated by Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103 positioned along a shallow trench in the longitudinal axis of ''Cf''CBM14 (Figure 1C and D). Mutational studies showed that binding to (GlcNAc)6 was abolished by mutation of Trp100 and Asp102. The main interaction is reported to be a CH-π stacking between Trp100 and GlcNAc-5 aided by Met51 and Pro53 which are both in van der Waal distances to GlcNAc-1 and GlcNAc-3, respectively <cite>Hurlburt2018</cite>. Although equivalents to Trp100, Asp102 and Tyr103 have been reported to be important for chitin-binding in CBM14 from tomato pathogen ''P. fuligena'' (''Pf''CBM14) (equivalent residues: Trp94, Asp96 and Tyr97) <cite>Kohler2016</cite>, the extensive hydrogen bond network could point to a different binding mechanism for ''Cf''CBM14 that is more reminiscent of a Type B CBM.
== Functionalities ==
Several members of CBM14 are often encountered as chitin-binding lectins <cite>Kawabata1996 Burg2004 Suetake2000 Kohler2016 Hurlburt2018</cite>, while the members present in modular chitinases play a key role in targeting substrate. The most common associated modules are chitinases, e.g. [[GH18]] from human chitotriosidase structurally determined together with CBM14CHIT1 (PDB ID: [https://www.rcsb.org/structure/5HBF 5HBF])<cite>Fadel2016</cite>.

Although some of the structural features described above differ between the lectin-CBM14 and CBM14CHIT1, the common denominator is the involvement of these modules in immune responses. CHIT1 is produced by macrophages and neutrophils <cite>Hollak1994, Kzhyshkowska2007</cite> and is utilized by innate immune response to combat chitin-containing pathogens <cite>Gordon-Thomson2009</cite>. A similar response is found in the tomato pathogen ''C. fulvum''. Here, the effector protein utilizes CBM14's ability to bind chitin in the fungal cell wall enabling protection from hydrolysis by plant-derived chitinases during infection <cite>Joosten1997 Burg2006</cite>.
== Family Firsts ==
;First Identified
:CBM14 was first identified as an antimicrobial lectin-like protein with chitin binding ability in the hemocyte of horseshoe crab (''Tachypleus tridentatus'') and called tachycitin <cite>Kawabata1996</cite>.
;First Structural Characterization
:The first three-dimensional structure was determined by NMR spectroscopy for the CBM14 module tachycitin (PDB ID: [https://www.rcsb.org/structure/1DQC 1DQC]) <cite>Suetake2000</cite>. The structure of the first carbohydrate-active enzyme associated CBM14 was determined by X-ray crystallography for the CBM14 of human chitotriosidase (PDB ID: [https://www.rcsb.org/structure/5HBF 5HBF]) <cite>Fadel2016</cite>.

== References ==
<biblio>
#Fadel2016 pmid=27111557
#Kohler2016 pmid=27401545
#Hurlburt2018 pmid=30148881
#Kawabata1996 pmid=9010778
#Shen1998 pmid=9651363
#Vandevenne2011 pmid=21674664
#Madland2019 pmid=31891077
#Crasson2016 pmid=28584264
#Suetake2000 pmid=10770921
#Boraston2004 pmid=15214846

#Burg2004 pmid=14769793
#Hollak1994 pmid=8132768
#Kzhyshkowska2007 pmid=19662198
#Gordon-Thomson2009 pmid=19169854
#Joosten1997 pmid=9090881
#Burg2006 pmid=17153926
</biblio>

[[Category:Carbohydrate Binding Module Families|CBM014]]

Carbohydrate Binding Module Family 14

2020-11-27T14:48:01Z

Eva Madland:

{{UnderConstruction}}
* [[Author]]: ^^^Eva Madland^^^
* [[Responsible Curator]]: ^^^Elizabeth Ficko-Blean^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBMnn.html
|}
</div>


== Ligand specificities ==
Family 14 CBMs are modules composed of approximately 70 residues. These modules have been reported to be associated with chitinases <cite>Fadel2016</cite> and as chitin-binding lectins e.g. an effector protein from the tomato pathogen ''Pseudoercospora fuligena'' or ''Cladosporium fulvum'' <cite>Kohler2016 Hurlburt2018</cite>, as an antimicrobial lectin-like protein (tachycitin) from horseshoe crab hemocytes <cite>Kawabata1996</cite> and in peritrophic matrix proteins from Malaria vector ''Anopheles gambia'' <cite>Shen1998</cite>. Members of CBM14 have been shown to bind chitin <cite>Shen1998 Vandevenne2011 Madland2019</cite> and chitooligomers <cite>Crasson2016 Hurlburt2018</cite>. Binding to 50 % acetylated hyaluronan has also been demonstrated <cite>Crasson2016</cite>.

The ligand binding affinities have been quantified for two CBM14 members. The interaction between a human chitotriosidase-1 (CHIT1, characterized as a glycoside hydrolase family 18 ([[GH18]])) CBM14 and (GlcNAc)3 have been investigated with NMR titration experiments and isothermal titration calorimetry (ITC) displaying a relatively weak interaction of Kd 9.9 ± 0.8 mM <cite>Crasson2016</cite> and Kd 3.1 ± 0.2 mM <cite>Madland2019</cite>, respectively.

Interaction studies have also been performed for CBM14 in the fungal tomato pathogen ''C. fulvum'' and (GlcNAc)6. Here, the binding properties were measured using ITC yielding a Kd of 6.7 ± 1.5 µM <cite>Hurlburt2018</cite>.

== Structural Features ==
[[File:Fig1-cbm14.png|300px|right|'''Figure X.''' Figure legend.]]

The structures of CBM14 members have a hevein-like fold commonly made up by a central β-sheet (three anti-parallel β-strands) linked to a small β-sheet (two anti-parallel β-strands) by two aromatic residues. The CBM14 members from tomato pathogens also have an N-terminal α-helix and an extended loop connecting -strands 2 and 3, as well as a C-terminal helical turn <cite>Kohler2016 Hurlburt2018</cite>. The latter is also present in tachycitin <cite>Suetake2000</cite>. In addtion, the CBM14 structures have been reported to contain 3-4 disulfide bridges which also serve as a stabilizing effect on this unique fold <cite>Suetake2000 Fadel2016 Hurlburt2018</cite>.
With this hevein-like fold and lectin properties, CBM14 is characterized as a Type C CBM <cite>Boraston2004</cite>. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (CBM14CHIT1). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of this module <cite>Crasson2016</cite> (Figure 1A). These residues create a platform-like binding surface (Figure 1B) commonly seen in Type A CBMs and could be the reason for why CBM14CHIT1 also is able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) have been reported <cite>Madland2019</cite> to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465. Binding between CBM14CHIT1 and chitotriose is likely to occur through CH-π stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end <cite>Madland2019</cite>.

CBM14 from the tomato pathogen ''C. fulvum'' (''Cf''CBM14) was the first of these modules to be co-crystallized with (GlcNAc)6 (PDB ID: [https://www.rcsb.org/structure/6BN0 6BN0])<cite>Hurlburt2018</cite>. Although the fold of ''Cf''CBM14 is the same as CBM14CHIT1 and other [http://www.cazy.org/CBM14_structure.html structurally characterized CBM14 members], the residues responsible for binding differ. Binding of (GlcNAc)6 is mediated by Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103 positioned along a shallow trench in the longitudinal axis of ''Cf''CBM14 (Figure 1C and D). Mutational studies showed that binding to (GlcNAc)6 was abolished by mutation of Trp100 and Asp102. The main interaction is reported to be a CH-π stacking between Trp100 and GlcNAc-5 aided by Met51 and Pro53 which are both in van der Waal distances to GlcNAc-1 and GlcNAc-3, respectively <cite>Hurlburt2018</cite>. Although equivalents to Trp100, Asp102 and Tyr103 have been reported to be important for chitin-binding in CBM14 from tomato pathogen ''P. fuligena'' (''Pf''CBM14) (equivalent residues: Trp94, Asp96 and Tyr97) <cite>Kohler2016</cite>, the extensive hydrogen bond network could point to a different binding mechanism for ''Cf''CBM14 that is more reminiscent of a Type B CBM.
== Functionalities ==
Several members of CBM14 are often encountered as chitin-binding lectins <cite>Kawabata1996 Burg2004 Suetake2000 Kohler2016 Hurlburt2018</cite>, while the members present in modular chitinases play a key role in targeting substrate. The most common associated modules are chitinases, e.g. [[GH18]] from human chitotriosidase structurally determined together with CBM14CHIT1 (PDB ID: [https://www.rcsb.org/structure/5HBF 5HBF])<cite>Fadel2016</cite>.

Although some of the structural features described above differ between the lectin-CBM14 and CBM14CHIT1, the common denominator is the involvement of these modules in immune responses. CHIT1 is produced by macrophages and neutrophils <cite>Hollak1994, Kzhyshkowska2007</cite> and is utilized by innate immune response to combat chitin-containing pathogens <cite>Gordon-Thomson2009</cite>. A similar response is found in the tomato pathogen ''C. fulvum''. Here, the effector protein utilizes CBM14's ability to bind chitin in the fungal cell wall enabling protection from hydrolysis by plant-derived chitinases during infection <cite>Joosten1997 Burg2006</cite>.
== Family Firsts ==
;First Identified
:CBM14 was first identified as an antimicrobial lectin-like protein with chitin binding ability in the hemocyte of horseshoe crab (''Tachypleus tridentatus'') and called tachycitin <cite>Kawabata1996</cite>.
;First Structural Characterization
:The first three-dimensional structure was determined by NMR spectroscopy for the CBM14 module tachycitin <cite>Suetake2000</cite>. The structure of the first carbohydrate-active enzyme associated CBM14 was determined by X-ray crystallography for the CBM14 of human chitotriosidase <cite>Fadel2016</cite>.

== References ==
<biblio>
#Fadel2016 pmid=27111557
#Kohler2016 pmid=27401545
#Hurlburt2018 pmid=30148881
#Kawabata1996 pmid=9010778
#Shen1998 pmid=9651363
#Vandevenne2011 pmid=21674664
#Madland2019 pmid=31891077
#Crasson2016 pmid=28584264
#Suetake2000 pmid=10770921
#Boraston2004 pmid=15214846

#Burg2004 pmid=14769793
#Hollak1994 pmid=8132768
#Kzhyshkowska2007 pmid=19662198
#Gordon-Thomson2009 pmid=19169854
#Joosten1997 pmid=9090881
#Burg2006 pmid=17153926
</biblio>

[[Category:Carbohydrate Binding Module Families|CBM014]]

Carbohydrate Binding Module Family 14

2020-11-27T14:42:06Z

Eva Madland:

{{UnderConstruction}}
* [[Author]]: ^^^Eva Madland^^^
* [[Responsible Curator]]: ^^^Elizabeth Ficko-Blean^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBMnn.html
|}
</div>


== Ligand specificities ==
Family 14 CBMs are modules composed of approximately 70 residues. These modules have been reported to be associated with chitinases <cite>Fadel2016</cite> and as chitin-binding lectins e.g. an effector protein from the tomato pathogen ''Pseudoercospora fuligena'' or ''Cladosporium fulvum'' <cite>Kohler2016 Hurlburt2018</cite>, as an antimicrobial lectin-like protein (tachycitin) from horseshoe crab hemocytes <cite>Kawabata1996</cite> and in peritrophic matrix proteins from Malaria vector ''Anopheles gambia'' <cite>Shen1998</cite>. Members of CBM14 have been shown to bind chitin <cite>Shen1998 Vandevenne2011 Madland2019</cite> and chitooligomers <cite>Crasson2016 Hurlburt2018</cite>. Binding to 50 % acetylated hyaluronan has also been demonstrated <cite>Crasson2016</cite>.

The ligand binding affinities have been quantified for two CBM14 members. The interaction between a human chitotriosidase-1 (CHIT1, characterized as a glycoside hydrolase family 18 ([[GH18]])) CBM14 and (GlcNAc)3 have been investigated with NMR titration experiments and isothermal titration calorimetry (ITC) displaying a relatively weak interaction of Kd 9.9 ± 0.8 mM <cite>Crasson2016</cite> and Kd 3.1 ± 0.2 mM <cite>Madland2019</cite>, respectively.

Interaction studies have also been performed for CBM14 in the fungal tomato pathogen ''C. fulvum'' and (GlcNAc)6. Here, the binding properties were measured using ITC yielding a Kd of 6.7 ± 1.5 µM <cite>Hurlburt2018</cite>.

== Structural Features ==
[[File:Fig1-cbm14.png|300px|right]]

The structures of CBM14 members have a hevein-like fold commonly made up by a central β-sheet (three anti-parallel β-strands) linked to a small β-sheet (two anti-parallel β-strands) by two aromatic residues. The CBM14 members from tomato pathogens also have an N-terminal α-helix and an extended loop connecting -strands 2 and 3, as well as a C-terminal helical turn <cite>Kohler2016 Hurlburt2018</cite>. The latter is also present in tachycitin <cite>Suetake2000</cite>. In addtion, the CBM14 structures have been reported to contain 3-4 disulfide bridges which also serve as a stabilizing effect on this unique fold <cite>Suetake2000 Fadel2016 Hurlburt2018</cite>.
With this hevein-like fold and lectin properties, CBM14 is characterized as a Type C CBM <cite>Boraston2004</cite>. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (CBM14CHIT1). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of this module <cite>Crasson2016</cite> (Figure 1A). These residues create a platform-like binding surface (Figure 1B) commonly seen in Type A CBMs and could be the reason for why CBM14CHIT1 also is able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) have been reported <cite>Madland2019</cite> to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465. Binding between CBM14CHIT1 and chitotriose is likely to occur through CH-π stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end <cite>Madland2019</cite>.

CBM14 from the tomato pathogen ''C. fulvum'' (''Cf''CBM14) was the first of these modules to be co-crystallized with (GlcNAc)6 (PDB ID: [https://www.rcsb.org/structure/6BN0 6BN0])<cite>Hurlburt2018</cite>. Although the fold of ''Cf''CBM14 is the same as CBM14CHIT1 and other [http://www.cazy.org/CBM14_structure.html structurally characterized CBM14 members], the residues responsible for binding differ. Binding of (GlcNAc)6 is mediated by Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103 positioned along a shallow trench in the longitudinal axis of ''Cf''CBM14 (Figure 1C and D). Mutational studies showed that binding to (GlcNAc)6 was abolished by mutation of Trp100 and Asp102. The main interaction is reported to be a CH-π stacking between Trp100 and GlcNAc-5 aided by Met51 and Pro53 which are both in van der Waal distances to GlcNAc-1 and GlcNAc-3, respectively <cite>Hurlburt2018</cite>. Although equivalents to Trp100, Asp102 and Tyr103 have been reported to be important for chitin-binding in CBM14 from tomato pathogen ''P. fuligena'' (''Pf''CBM14) (equivalent residues: Trp94, Asp96 and Tyr97) <cite>Kohler2016</cite>, the extensive hydrogen bond network could point to a different binding mechanism for ''Cf''CBM14 that is more reminiscent of a Type B CBM.
== Functionalities ==
Several members of CBM14 are often encountered as chitin-binding lectins <cite>Kawabata1996 Burg2004 Suetake2000 Kohler2016 Hurlburt2018</cite>, while the members present in modular chitinases play a key role in targeting substrate. The most common associated modules are chitinases, e.g. [[GH18]] from human chitotriosidase structurally determined together with CBM14CHIT1 (PDB ID: [https://www.rcsb.org/structure/5HBF 5HBF])<cite>Fadel2016</cite>.

Although some of the structural features described above differ between the lectin-CBM14 and CBM14CHIT1, the common denominator is the involvement of these modules in immune responses. CHIT1 is produced by macrophages and neutrophils <cite>Hollak1994, Kzhyshkowska2007</cite> and is utilized by innate immune response to combat chitin-containing pathogens <cite>Gordon-Thomson2009</cite>. A similar response is found in the tomato pathogen ''C. fulvum''. Here, the effector protein utilizes CBM14's ability to bind chitin in the fungal cell wall enabling protection from hydrolysis by plant-derived chitinases during infection <cite>Joosten1997 Burg2006</cite>.
== Family Firsts ==
;First Identified
:CBM14 was first identified as an antimicrobial lectin-like protein with chitin binding ability in the hemocyte of horseshoe crab (''Tachypleus tridentatus'') and called tachycitin <cite>Kawabata1996</cite>.
;First Structural Characterization
:The first three-dimensional structure was determined by NMR spectroscopy for the CBM14 module tachycitin <cite>Suetake2000</cite>. The structure of the first carbohydrate-active enzyme associated CBM14 was determined by X-ray crystallography for the CBM14 of human chitotriosidase <cite>Fadel2016</cite>.

== References ==
<biblio>
#Fadel2016 pmid=27111557
#Kohler2016 pmid=27401545
#Hurlburt2018 pmid=30148881
#Kawabata1996 pmid=9010778
#Shen1998 pmid=9651363
#Vandevenne2011 pmid=21674664
#Madland2019 pmid=31891077
#Crasson2016 pmid=28584264
#Suetake2000 pmid=10770921
#Boraston2004 pmid=15214846

#Burg2004 pmid=14769793
#Hollak1994 pmid=8132768
#Kzhyshkowska2007 pmid=19662198
#Gordon-Thomson2009 pmid=19169854
#Joosten1997 pmid=9090881
#Burg2006 pmid=17153926
</biblio>

[[Category:Carbohydrate Binding Module Families|CBM014]]

File:Fig1-cbm14.png

2020-11-27T14:36:07Z

Eva Madland:

Carbohydrate Binding Module Family 14

2020-11-27T14:34:24Z

Eva Madland:

{{UnderConstruction}}
* [[Author]]: ^^^Eva Madland^^^
* [[Responsible Curator]]: ^^^Elizabeth Ficko-Blean^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBMnn.html
|}
</div>


== Ligand specificities ==
Family 14 CBMs are modules composed of approximately 70 residues. These modules have been reported to be associated with chitinases <cite>Fadel2016</cite> and as chitin-binding lectins e.g. an effector protein from the tomato pathogen ''Pseudoercospora fuligena'' or ''Cladosporium fulvum'' <cite>Kohler2016 Hurlburt2018</cite>, as an antimicrobial lectin-like protein (tachycitin) from horseshoe crab hemocytes <cite>Kawabata1996</cite> and in peritrophic matrix proteins from Malaria vector ''Anopheles gambia'' <cite>Shen1998</cite>. Members of CBM14 have been shown to bind chitin <cite>Shen1998 Vandevenne2011 Madland2019</cite> and chitooligomers <cite>Crasson2016 Hurlburt2018</cite>. Binding to 50 % acetylated hyaluronan has also been demonstrated <cite>Crasson2016</cite>.

The ligand binding affinities have been quantified for two CBM14 members. The interaction between a human chitotriosidase-1 (CHIT1, characterized as a glycoside hydrolase family 18 ([[GH18]])) CBM14 and (GlcNAc)3 have been investigated with NMR titration experiments and isothermal titration calorimetry (ITC) displaying a relatively weak interaction of Kd 9.9 ± 0.8 mM <cite>Crasson2016</cite> and Kd 3.1 ± 0.2 mM <cite>Madland2019</cite>, respectively.

Interaction studies have also been performed for CBM14 in the fungal tomato pathogen ''C. fulvum'' and (GlcNAc)6. Here, the binding properties were measured using ITC yielding a Kd of 6.7 ± 1.5 µM <cite>Hurlburt2018</cite>.

== Structural Features ==
The structures of CBM14 members have a hevein-like fold commonly made up by a central β-sheet (three anti-parallel β-strands) linked to a small β-sheet (two anti-parallel β-strands) by two aromatic residues. The CBM14 members from tomato pathogens also have an N-terminal α-helix and an extended loop connecting -strands 2 and 3, as well as a C-terminal helical turn <cite>Kohler2016 Hurlburt2018</cite>. The latter is also present in tachycitin <cite>Suetake2000</cite>. In addtion, the CBM14 structures have been reported to contain 3-4 disulfide bridges which also serve as a stabilizing effect on this unique fold <cite>Suetake2000 Fadel2016 Hurlburt2018</cite>.

With this hevein-like fold and lectin properties, CBM14 is characterized as a Type C CBM <cite>Boraston2004</cite>. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (CBM14CHIT1). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of this module <cite>Crasson2016</cite>. These residues create a platform-like binding surface commonly seen in Type A CBMs and could be the reason for why CBM14CHIT1 also is able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) have been reported <cite>Madland2019</cite> to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465. Binding between CBM14CHIT1 and chitotriose is likely to occur through CH-π stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end <cite>Madland2019</cite>.

CBM14 from the tomato pathogen ''C. fulvum'' (''Cf''CBM14) was the first of these modules to be co-crystallized with (GlcNAc)6 (PDB ID: [https://www.rcsb.org/structure/6BN0 6BN0])<cite>Hurlburt2018</cite>. Although the fold of ''Cf''CBM14 is the same as CBM14CHIT1 and other [http://www.cazy.org/CBM14_structure.html structurally characterized CBM14 members], the residues responsible for binding differ. Binding of (GlcNAc)6 is mediated by Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103 positioned along a shallow trench in the longitudinal axis of ''Cf''CBM14. Mutational studies showed that binding to (GlcNAc)6 was abolished by mutation of Trp100 and Asp102. The main interaction is reported to be a CH-π stacking between Trp100 and GlcNAc-5 aided by Met51 and Pro53 which are both in van der Waal distances to GlcNAc-1 and GlcNAc-3, respectively <cite>Hurlburt2018</cite>. Although equivalents to Trp100, Asp102 and Tyr103 have been reported to be important for chitin-binding in CBM14 from tomato pathogen ''P. fuligena'' (''Pf''CBM14) (equivalent residues: Trp94, Asp96 and Tyr97) <cite>Kohler2016</cite>, the extensive hydrogen bond network could point to a different binding mechanism for ''Cf''CBM14 that is more reminiscent of a Type B CBM.
== Functionalities ==
Several members of CBM14 are often encountered as chitin-binding lectins <cite>Kawabata1996 Burg2004 Suetake2000 Kohler2016 Hurlburt2018</cite>, while the members present in modular chitinases play a key role in targeting substrate. The most common associated modules are chitinases, e.g. [[GH18]] from human chitotriosidase structurally determined together with CBM14CHIT1 (PDB ID: [https://www.rcsb.org/structure/5HBF 5HBF])<cite>Fadel2016</cite>.

Although some of the structural features described above differ between the lectin-CBM14 and CBM14CHIT1, the common denominator is the involvement of these modules in immune responses. CHIT1 is produced by macrophages and neutrophils <cite>Hollak1994, Kzhyshkowska2007</cite> and is utilized by innate immune response to combat chitin-containing pathogens <cite>Gordon-Thomson2009</cite>. A similar response is found in the tomato pathogen ''C. fulvum''. Here, the effector protein utilizes CBM14's ability to bind chitin in the fungal cell wall enabling protection from hydrolysis by plant-derived chitinases during infection <cite>Joosten1997 Burg2006</cite>.
== Family Firsts ==
;First Identified
:CBM14 was first identified as an antimicrobial lectin-like protein with chitin binding ability in the hemocyte of horseshoe crab (''Tachypleus tridentatus'') and called tachycitin <cite>Kawabata1996</cite>.
;First Structural Characterization
:The first three-dimensional structure was determined by NMR spectroscopy for the CBM14 module tachycitin <cite>Suetake2000</cite>. The structure of the first carbohydrate-active enzyme associated CBM14 was determined by X-ray crystallography for the CBM14 of human chitotriosidase <cite>Fadel2016</cite>.

== References ==
<biblio>
#Fadel2016 pmid=27111557
#Kohler2016 pmid=27401545
#Hurlburt2018 pmid=30148881
#Kawabata1996 pmid=9010778
#Shen1998 pmid=9651363
#Vandevenne2011 pmid=21674664
#Madland2019 pmid=31891077
#Crasson2016 pmid=28584264
#Suetake2000 pmid=10770921
#Boraston2004 pmid=15214846

#Burg2004 pmid=14769793
#Hollak1994 pmid=8132768
#Kzhyshkowska2007 pmid=19662198
#Gordon-Thomson2009 pmid=19169854
#Joosten1997 pmid=9090881
#Burg2006 pmid=17153926
</biblio>

[[Category:Carbohydrate Binding Module Families|CBM014]]

Carbohydrate Binding Module Family 14

2020-11-27T14:26:34Z

Eva Madland:

{{UnderConstruction}}
* [[Author]]: ^^^Eva Madland^^^
* [[Responsible Curator]]: ^^^Elizabeth Ficko-Blean^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBMnn.html
|}
</div>


== Ligand specificities ==
Family 14 CBMs are modules composed of approximately 70 residues. These modules have been reported to be associated with chitinases <cite>Fadel2016</cite> and as chitin-binding lectins e.g. an effector protein from the tomato pathogen ''Pseudoercospora fuligena'' or ''Cladosporium fulvum'' <cite>Kohler2016 Hurlburt2018</cite>, as an antimicrobial lectin-like protein (tachycitin) from horseshoe crab haemocytes <cite>Kawabata1996</cite> and in peritrophic matrix proteins from Malaria vector ''Anopheles gambia'' <cite>Shen1998</cite>. Members of CBM14 have been shown to bind chitin <cite>Shen1998 Vandevenne2011 Madland2019</cite> and chitooligomers <cite>Crasson2016 Hurlburt2018</cite>. Binding to 50 % acetylated hyaluronan has also been demonstrated <cite>Crasson2016</cite>.

The ligand binding affinities have been quantified for two CBM14 members. The interaction between a human chitotriosidase-1 (CHIT1, characterized as a glycoside hydrolase family 18 ([[GH18]])) CBM14 and (GlcNAc)3 have been investigated with NMR titration experiments and isothermal titration calorimetry (ITC) displaying a relatively weak interaction of Kd 9.9 ± 0.8 mM <cite>Crasson2016</cite> and Kd 3.1 ± 0.2 mM <cite>Madland2019</cite>, respectively.

Interaction studies have also been performed for CBM14 in the fungal tomato pathogen ''C. fulvum'' and (GlcNAc)6. Here, the binding properties were measured using ITC yielding a Kd of 6.7 ± 1.5 µM <cite>Hurlburt2018</cite>.

== Structural Features ==
The structures of CBM14 members have a hevein-like fold commonly made up by a central β-sheet (three anti-parallel β-strands) linked to a small β-sheet (two anti-parallel β-strands) by two aromatic residues. The CBM14 members from tomato pathogens also have an N-terminal α-helix and an extended loop connecting -strands 2 and 3, as well as a C-terminal helical turn <cite>Kohler2016 Hurlburt2018</cite>. The latter is also present in tachycitin <cite>Suetake2000</cite>. In addtion, the CBM14 structures have been reported to contain 3-4 disulfide bridges which also serve as a stabilizing effect on this unique fold <cite>Suetake2000 Fadel2016 Hurlburt2018</cite>.

With this hevein-like fold and lectin properties, CBM14 is characterized as a Type C CBM <cite>Boraston2004</cite>. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (CBM14CHIT1). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of this module <cite>Crasson2016</cite>. These residues create a platform-like binding surface commonly seen in Type A CBMs and could be the reason for why CBM14CHIT1 also is able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) have been reported <cite>Madland2019</cite> to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465. Binding between CBM14CHIT1 and chitotriose is likely to occur through CH-π stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end <cite>Madland2019</cite>.

CBM14 from the tomato pathogen ''C. fulvum'' (''Cf''CBM14) was the first of these modules to be co-crystallized with (GlcNAc)6 (PDB ID: [https://www.rcsb.org/structure/6BN0 6BN0])<cite>Hurlburt2018</cite>. Although the fold of ''Cf''CBM14 is the same as CBM14CHIT1 and other [http://www.cazy.org/CBM14_structure.html structurally characterized CBM14 members], the residues responsible for binding differ. Binding of (GlcNAc)6 is mediated by Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103 positioned along a shallow trench in the longitudinal axis of ''Cf''CBM14. Mutational studies showed that binding to (GlcNAc)6 was abolished by mutation of Trp100 and Asp102. The main interaction is reported to be a CH-π stacking between Trp100 and GlcNAc-5 aided by Met51 and Pro53 which are both in van der Waal distances to GlcNAc-1 and GlcNAc-3, respectively <cite>Hurlburt2018</cite>. Although equivalents to Trp100, Asp102 and Tyr103 have been reported to be important for chitin-binding in CBM14 from tomato pathogen ''P. fuligena'' (''Pf''CBM14) (equivalent residues: Trp94, Asp96 and Tyr97) <cite>Kohler2016</cite>, the extensive hydrogen bond network could point to a different binding mechanism for ''Cf''CBM14 that is more reminiscent of a Type B CBM.
== Functionalities ==
Several members of CBM14 are often encountered as chitin-binding lectins <cite>Kawabata1996 Burg2004 Suetake2000 Kohler2016 Hurlburt2018</cite>, while the members present in modular chitinases play a key role in targeting substrate. The most common associated modules are chitinases, e.g. [[GH18]] from human chitotriosidase structurally determined together with CBM14CHIT1 (PDB ID: [https://www.rcsb.org/structure/5HBF 5HBF])<cite>Fadel2016</cite>.

Although some of the structural features described above differ between the lectin-CBM14 and CBM14CHIT1, the common denominator is the involvement of these modules in immune responses. CHIT1 is produced by macrophages and neutrophils <cite>Hollak1994, Kzhyshkowska2007</cite> and is utilized by innate immune response to combat chitin-containing pathogens <cite>Gordon-Thomson2009</cite>. A similar response is found in the tomato pathogen ''C. fulvum''. Here, the effector protein utilizes CBM14's ability to bind chitin in the fungal cell wall enabling protection from hydrolysis by plant-derived chitinases during infection <cite>Joosten1997 Burg2006</cite>.
== Family Firsts ==
;First Identified
:Insert archetype here, possibly including ''very brief'' synopsis.
;First Structural Characterization
:Insert archetype here, possibly including ''very brief'' synopsis.

== References ==
<biblio>
#Fadel2016 pmid=27111557
#Kohler2016 pmid=27401545
#Hurlburt2018 pmid=30148881
#Kawabata1996 pmid=9010778
#Shen1998 pmid=9651363
#Vandevenne2011 pmid=21674664
#Madland2019 pmid=31891077
#Crasson2016 pmid=28584264
#Suetake2000 pmid=10770921
#Boraston2004 pmid=15214846

#Burg2004 pmid=14769793
#Hollak1994 pmid=8132768
#Kzhyshkowska2007 pmid=19662198
#Gordon-Thomson2009 pmid=19169854
#Joosten1997 pmid=9090881
#Burg2006 pmid=17153926
</biblio>

[[Category:Carbohydrate Binding Module Families|CBM014]]

Carbohydrate Binding Module Family 14

2020-11-27T14:12:22Z

Eva Madland:

{{UnderConstruction}}
* [[Author]]: ^^^Eva Madland^^^
* [[Responsible Curator]]: ^^^Elizabeth Ficko-Blean^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBMnn.html
|}
</div>


== Ligand specificities ==
Family 14 CBMs are modules composed of approximately 70 residues. These modules have been reported to be associated with chitinases <cite>Fadel2016</cite> and as chitin-binding lectins e.g. an effector protein from the tomato pathogen ''Pseudoercospora fuligena'' or ''Cladosporium fulvum'' <cite>Kohler2016 Hurlburt2018</cite>, as an antimicrobial lectin-like protein (tachycitin) from horseshoe crab haemocytes <cite>Kawabata1996</cite> and in peritrophic matrix proteins from Malaria vector ''Anopheles gambia'' <cite>Shen1998</cite>. Members of CBM14 have been shown to bind chitin <cite>Shen1998 Vandevenne2011 Madland2019</cite> and chitooligomers <cite>Crasson2016 Hurlburt2018</cite>. Binding to 50 % acetylated hyaluronan has also been demonstrated <cite>Crasson2016</cite>.

The ligand binding affinities have been quantified for two CBM14 members. The interaction between a human chitotriosidase-1 (CHIT1, characterized as a glycoside hydrolase family 18 ([[GH18]])) CBM14 and (GlcNAc)3 have been investigated with NMR titration experiments and isothermal titration calorimetry (ITC) displaying a relatively weak interaction of Kd 9.9 ± 0.8 mM <cite>Crasson2016</cite> and Kd 3.1 ± 0.2 mM <cite>Madland2019</cite>, respectively.

Interaction studies have also been performed for CBM14 in the fungal tomato pathogen ''C. fulvum'' and (GlcNAc)6. Here, the binding properties were measured using ITC yielding a Kd of 6.7 ± 1.5 µM <cite>Hurlburt2018</cite>.

== Structural Features ==
The structures of CBM14 members have a hevein-like fold commonly made up by a central β-sheet (three anti-parallel β-strands) linked to a small β-sheet (two anti-parallel β-strands) by two aromatic residues. The CBM14 members from tomato pathogens also have an N-terminal α-helix and an extended loop connecting -strands 2 and 3, as well as a C-terminal helical turn <cite>Kohler2016 Hurlburt2018</cite>. The latter is also present in tachycitin <cite>Suetake2000</cite>. In addtion, the CBM14 structures have been reported to contain 3-4 disulfide bridges which also serve as a stabilizing effect on this unique fold <cite>Suetake2000 Fadel2016 Hurlburt2018</cite>.

With this hevein-like fold and lectin properties, CBM14 is characterized as a Type C CBM <cite>Boraston2004</cite>. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (CBM14CHIT1). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of this module <cite>Crasson2016</cite>. These residues create a platform-like binding surface commonly seen in Type A CBMs and could be the reason for why CBM14CHIT1 also is able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) have been reported <cite>Madland2019</cite> to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465. Binding between CBM14CHIT1 and chitotriose is likely to occur through CH-π stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end <cite>Madland2019</cite>.

CBM14 from the tomato pathogen ''C. fulvum'' (''Cf''CBM14) was the first of these modules to be co-crystallized with (GlcNAc)6 <cite>Hurlburt2018</cite>. Although the fold of ''Cf''CBM14 is the same as CBM14CHIT1 and other [http://www.cazy.org/CBM14_structure.html structurally characterized CBM14 members], the residues responsible for binding differ. Binding of (GlcNAc)6 is mediated by Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103 positioned along a shallow trench in the longitudinal axis of ''Cf''CBM14. Mutational studies showed that binding to (GlcNAc)6 was abolished by mutation of Trp100 and Asp102. The main interaction is reported to be a CH-π stacking between Trp100 and GlcNAc-5 aided by Met51 and Pro53 which are both in van der Waal distances to GlcNAc-1 and GlcNAc-3, respectively <cite>Hurlburt2018</cite>. Although equivalents to Trp100, Asp102 and Tyr103 have been reported to be important for chitin-binding in CBM14 from tomato pathogen ''P. fuligena'' (''Pf''CBM14) (equivalent residues: Trp94, Asp96 and Tyr97) <cite>Kohler2016</cite>, the extensive hydrogen bond network could point to a different binding mechanism for ''Cf''CBM14 that is more reminiscent of a Type B CBM.
== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' Describe common functional roles such as targeting, disruptive, anchoring, proximity/position on substrate.
* '''Most Common Associated Modules:''' 1. Glycoside Hydrolase Activity; 2. Additional Associated Modules (other CBM, FNIII, cohesin, dockerins, expansins, etc.)
* '''Novel Applications:''' Include here if CBM has been used to modify another enzyme, or if a CBM was used to label plant/mammalian tissues? Etc.

== Family Firsts ==
;First Identified
:Insert archetype here, possibly including ''very brief'' synopsis.
;First Structural Characterization
:Insert archetype here, possibly including ''very brief'' synopsis.

== References ==
<biblio>
#Fadel2016 pmid=27111557
#Kohler2016 pmid=27401545
#Hurlburt2018 pmid=30148881
#Kawabata1996 pmid=9010778
#Shen1998 pmid=9651363
#Vandevenne2011 pmid=21674664
#Madland2019 pmid=31891077
#Crasson2016 pmid=28584264
#Suetake2000 pmid=10770921
#Boraston2004 pmid=15214846

#Burg2004 pmid=14769793
#Hollak1994 pmid=8132768
#Kzhyshkowska2007 pmid=19662198
#Gordon-Thomson2009 pmid=19169854
#Joosten1997 pmid=9090881
#Burg2006 pmid=17153926
</biblio>

[[Category:Carbohydrate Binding Module Families|CBM014]]

Carbohydrate Binding Module Family 14

2020-11-27T14:09:00Z

Eva Madland:

{{UnderConstruction}}
* [[Author]]: ^^^Eva Madland^^^
* [[Responsible Curator]]: ^^^Elizabeth Ficko-Blean^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBMnn.html
|}
</div>


== Ligand specificities ==
Family 14 CBMs are modules composed of approximately 70 residues. These modules have been reported to be associated with chitinases <cite>Fadel2016</cite> and as chitin-binding lectins e.g. an effector protein from the tomato pathogen ''Pseudoercospora fuligena'' or ''Cladosporium fulvum'' <cite>Kohler2016 Hurlburt2018</cite>, as an antimicrobial lectin-like protein (tachycitin) from horseshoe crab haemocytes <cite>Kawabata1996</cite> and in peritrophic matrix proteins from Malaria vector ''Anopheles gambia'' <cite>Shen1998</cite>. Members of CBM14 have been shown to bind chitin <cite>Shen1998 Vandevenne2011 Madland2019</cite> and chitooligomers <cite>Crasson2016 Hurlburt2018</cite>. Binding to 50 % acetylated hyaluronan has also been demonstrated <cite>Crasson2016</cite>.

The ligand binding affinities have been quantified for two CBM14 members. The interaction between a human chitotriosidase-1 (CHIT1, characterized as a glycoside hydrolase family 18 ([[GH18]])) CBM14 and (GlcNAc)3 have been investigated with NMR titration experiments and isothermal titration calorimetry (ITC) displaying a relatively weak interaction of Kd 9.9 ± 0.8 mM <cite>Crasson2016</cite> and Kd 3.1 ± 0.2 mM <cite>Madland2019</cite>, respectively.

Interaction studies have also been performed for CBM14 in the fungal tomato pathogen ''C. fulvum'' and (GlcNAc)6. Here, the binding properties were measured using ITC yielding a Kd of 6.7 ± 1.5 µM <cite>Hurlburt2018</cite>.

== Structural Features ==
The structures of CBM14 members have a hevein-like fold commonly made up by a central β-sheet (three anti-parallel β-strands) linked to a small β-sheet (two anti-parallel β-strands) by two aromatic residues. The CBM14 members from tomato pathogens also have an N-terminal α-helix and an extended loop connecting -strands 2 and 3, as well as a C-terminal helical turn <cite>Kohler2016 Hurlburt2018</cite>. The latter is also present in tachycitin <cite>Suetake2000</cite>. In addtion, the CBM14 structures have been reported to contain 3-4 disulfide bridges which also serve as a stabilizing effect on this unique fold <cite>Suetake2000 Fadel2016 Hurlburt2018</cite>.

With this hevein-like fold and lectin properties, CBM14 is characterized as a Type C CBM <cite>Boraston2004</cite>. This is in line with the ligand-binding feature seen for the CBM14 associated with CHIT1 (CBM14CHIT1). The binding site is composed of a tryptophan and an asparagine (Trp465 and Asn466) at the C-terminus of this module <cite>Crasson2016</cite>. These residues create a platform-like binding surface commonly seen in Type A CBMs and could be the reason for why CBM14CHIT1 also is able to bind crystalline chitin. In addition to Trp465 and Asn466, a leucine (Leu454) have been reported <cite>Madland2019</cite> to be indirectly involved in binding as it contributes to maintaining a correct orientation for Trp465. Binding between CBM14CHIT1 and chitotriose is likely to occur through CH-π stacking between the side-chain of Trp465 and the middle pyranose ring and hydrogen bonds between the side-chain of Asn466 and the hydrophilic non-reducing end <cite>Madland2019</cite>.

CBM14 from the tomato pathogen ''C. fulvum'' (''Cf''CBM14) was the first of these modules to be co-crystallized with (GlcNAc)6 <cite>Hurlburt2018</cite>. Although the fold of ''Cf''CBM14 is the same as CBM14CHIT1 and other [http://www.cazy.org/CBM14_structure.html structurally characterized CBM14 members], the residues responsible for binding differ. Binding of (GlcNAc)6 is mediated by Lys49, Cys50, Met51, Pro53, Lys99, Trp100, Cys101, Asp102 and Tyr103 positioned along a shallow trench in the longitudinal axis of ''Cf''CBM14. Mutational studies showed that binding to (GlcNAc)6 was abolished by mutation of Trp100 and Asp102. The main interaction is reported to be a CH-π stacking between Trp100 and GlcNAc-5 aided by Met51 and Pro53 which are both in van der Waal distances to GlcNAc-1 and GlcNAc-3, respectively <cite>Hurlburt2018</cite>.
== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' Describe common functional roles such as targeting, disruptive, anchoring, proximity/position on substrate.
* '''Most Common Associated Modules:''' 1. Glycoside Hydrolase Activity; 2. Additional Associated Modules (other CBM, FNIII, cohesin, dockerins, expansins, etc.)
* '''Novel Applications:''' Include here if CBM has been used to modify another enzyme, or if a CBM was used to label plant/mammalian tissues? Etc.

== Family Firsts ==
;First Identified
:Insert archetype here, possibly including ''very brief'' synopsis.
;First Structural Characterization
:Insert archetype here, possibly including ''very brief'' synopsis.

== References ==
<biblio>
#Fadel2016 pmid=27111557
#Kohler2016 pmid=27401545
#Hurlburt2018 pmid=30148881
#Kawabata1996 pmid=9010778
#Shen1998 pmid=9651363
#Vandevenne2011 pmid=21674664
#Madland2019 pmid=31891077
#Crasson2016 pmid=28584264
#Suetake2000 pmid=10770921
#Boraston2004 pmid=15214846

#Burg2004 pmid=14769793
#Hollak1994 pmid=8132768
#Kzhyshkowska2007 pmid=19662198
#Gordon-Thomson2009 pmid=19169854
#Joosten1997 pmid=9090881
#Burg2006 pmid=17153926
</biblio>

[[Category:Carbohydrate Binding Module Families|CBM014]]

Carbohydrate Binding Module Family 14

2020-11-27T13:59:45Z

Eva Madland:

Carbohydrate Binding Module Family 14

2020-11-26T15:12:00Z

Eva Madland:

Carbohydrate Binding Module Family 14

2020-11-26T15:10:57Z

Eva Madland:

Carbohydrate Binding Module Family 14

2020-11-26T15:07:36Z

Eva Madland:

Carbohydrate Binding Module Family 14

2020-11-26T14:58:46Z

Eva Madland:

Carbohydrate Binding Module Family 14

2020-11-26T14:56:38Z

Eva Madland:

Carbohydrate Binding Module Family 14

2020-11-26T14:51:48Z

Eva Madland:

Carbohydrate Binding Module Family 14

2020-11-26T14:46:53Z

Eva Madland:

Carbohydrate Binding Module Family 14

2020-11-26T14:37:56Z

Eva Madland:

Carbohydrate Binding Module Family 14

2020-11-26T14:31:17Z

Eva Madland:

User:Eva Madland

2020-11-25T13:58:32Z

Eva Madland:

[[Image:Cazypedia_EM.jpg|200px|right]]

Eva Madland has a M.Sc. in organic chemistry from the Norwegian University of Science and Technology (Trondheim, Norway), where she worked on isolation, separation and structural elucidation of natural products from plants. In 2020 she completed her PhD in Biotechnology at the Norwegian University of Science and Technology (Trondheim, Norway) under the supervision by Professor [[User:Finn_Aachmann|Finn Lillelund Aachmann]] and Professor Morten Sørlie. The work focused on studying interactions between carbohydrate-binding modules and carbohydrates using NMR spectroscopy. Currently, she is continuing this work in the [https://folk.ntnu.no/aachmann/ Biopolymer NMR group] led by Professor [[User:Finn_Aachmann|Finn Lillelund Aachmann]].

She has worked on the following CBMs:
* [[CBM14]] from human chitotriosidase <cite>Madland2019</cite>
* [[CBM86]] from ''Roseburia intestinalis'' L1-82 <cite>Madland2018,Leth2020</cite>

----

<biblio>
#Madland2018 pmid=30244308

#Leth2020 pmid=31693302

#Madland2019 pmid=31891077
</biblio>


[[Category:Contributors|Madland,Eva]]

User:Eva Madland

2020-11-25T13:58:03Z

Eva Madland:

[[Image:Cazypedia_EM.jpg|200px|right]]

Eva Madland has a M.Sc. in organic chemistry from the Norwegian University of Science and Technology (Trondheim, Norway), where she worked on isolation, separation and structural elucidation of natural products from plants. In 2020 she completed her PhD in Biotechnology at the Norwegian University of Science and Technology (Trondheim, Norway) under the supervision by Professor [[User:Finn_Aachmann|Finn Lillelund Aachmann]] and Professor Morten Sørlie. The work focused on studying interactions between carbohydrate-binding modules and carbohydrates using NMR spectroscopy. Currently, she is continuing this work in the [https://folk.ntnu.no/aachmann/ Biopolymer NMR group] led by Professor [[User:Finn_Aachmann|Finn Lillelund Aachmann]].

She has worked on the following CBMs:
* [[CBM14]] from human chitotriosidase <cite>Madland2019</cite>
* [[CBM86]] from ''Roseburia intestinalis'' L1-82 <cite>Madland2018,Leth2020</cite>
* Please upload a picture of yourself using the "Upload file" link in the Toolbox section of the left menu, and then replace the Image filename with your own.

----

<biblio>
#Madland2018 pmid=30244308

#Leth2020 pmid=31693302

#Madland2019 pmid=31891077
</biblio>


[[Category:Contributors|Madland,Eva]]

File:Cazypedia EM.jpg

2020-11-25T13:54:43Z

Eva Madland:

User:Eva Madland

2020-11-25T13:36:04Z

Eva Madland:

[[Image:Blank_user-200px.png|200px|right]]

Eva Madland has a M.Sc. in organic chemistry from the Norwegian University of Science and Technology (Trondheim, Norway), where she worked on isolation, separation and structural elucidation of natural products from plants. In 2020 she completed her PhD in Biotechnology at the Norwegian University of Science and Technology (Trondheim, Norway) under the supervision by Professor [[User:Finn_Aachmann|Finn Lillelund Aachmann]] and Professor Morten Sørlie. The work focused on studying interactions between carbohydrate-binding modules and carbohydrates using NMR spectroscopy. Currently, she is continuing this work in the [https://folk.ntnu.no/aachmann/ Biopolymer NMR group] led by Professor [[User:Finn_Aachmann|Finn Lillelund Aachmann]].

She has worked on the following CBMs:
* [[CBM14]] from human chitotriosidase <cite>Madland2019</cite>
* [[CBM86]] from ''Roseburia intestinalis'' L1-82 <cite>Madland2018,Leth2020</cite>
* Please upload a picture of yourself using the "Upload file" link in the Toolbox section of the left menu, and then replace the Image filename with your own.

----

<biblio>
#Madland2018 pmid=30244308

#Leth2020 pmid=31693302

#Madland2019 pmid=31891077
</biblio>


[[Category:Contributors|Madland,Eva]]

User:Eva Madland

2020-11-25T13:28:20Z

Eva Madland:

[[Image:Blank_user-200px.png|200px|right]]

Eva Madland has a M.Sc. in organic chemistry from the Norwegian University of Science and Technology (Trondheim, Norway), where she worked on isolation, separation and structural elucidation of natural products from plants. In 2020 she completed her PhD in Biotechnology at the Norwegian University of Science and Technology (Trondheim, Norway) under the supervision by Professor [[User:Finn_Aachmann|Finn Lillelund Aachmann]] and Professor Morten Sørlie. The work focused on studying interactions between carbohydrate-binding modules and carbohydrates using NMR spectroscopy. Currently, she is continuing this work in the group of Professor [[User:Finn_Aachmann|Finn Lillelund Aachmann]].

She has worked on the following CBMs:
* [[CBM14]] from human chitotriosidase <cite>Madland2019</cite>
* [[CBM86]] from ''Roseburia intestinalis'' L1-82 <cite>Madland2018,Leth2020</cite>
* Please upload a picture of yourself using the "Upload file" link in the Toolbox section of the left menu, and then replace the Image filename with your own.

----

<biblio>
#Madland2018 pmid=30244308

#Leth2020 pmid=31693302

#Madland2019 pmid=31891077
</biblio>


[[Category:Contributors|Madland,Eva]]

User:Eva Madland

2020-11-25T13:17:21Z

Eva Madland:

[[Image:Blank_user-200px.png|200px|right]]
'''This is an empty template to help you get started with composing your User page.'''

Eva Madland has a M.Sc. in organic chemistry from the Norwegian University of Science and Technology (Trondheim, Norway), where she worked on isolation, separation and structural elucidation of natural products from plants. In 2020 she completed her PhD in Biotechnology at the Norwegian University of Science and Technology (Trondheim, Norway) supervised by Professor [[User:Finn_Aachmann|Finn Lillelund Aachmann]] and Professor Morten Sørlie. The work focused on studying interactions between carbohydrate-binding modules and carbohydrates using NMR spectroscopy. Currently, she is continuing this work in the group of Professor [[User:Finn_Aachmann|Finn Lillelund Aachmann]].

* See [[User:Gerlind_Sulzenbacher|Gerlin Sulzenbacher]] for an example. You may copy text from this example by opening the page in another browser window and clicking the "Edit" tab.
* Add your publications in the list below using PubMed IDs and cite them in the text like this <cite>Gilbert2008</cite>.
* Please upload a picture of yourself using the "Upload file" link in the Toolbox section of the left menu, and then replace the Image filename with your own.

''More specific help on these steps is available from the links under the "For contributors" section of the left page menu.''

----

<biblio>
#Gilbert2008 pmid=18430603

</biblio>


[[Category:Contributors|Madland,Eva]]