CAZypedia - User contributions [en-ca]

Glycoside Hydrolase Family 39

2017-12-14T05:52:07Z

Darryl Jones:

{{CuratorApproved}}

* [[Author]]s: ^^^Brian Rempel^^^ and ^^^Darryl Jones^^^
* [[Responsible Curator]]: ^^^Steve Withers^^^

----

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family 39'''
|-
|'''Clan'''
|GH-A
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH39.html
|}
</div>

==Substrate Specificities==
This [[glycoside hydrolase]] family predominantly consists of two known enzyme activities: β-xylosidase and α-L-iduronidase. Both enzyme activities cleave equatorial glycosidic bonds: the 'α' designation of α-iduronidase is a consequence of the stereochemical designations used for carbohydrates in which the α/β designation is related to the [[Absolute_configuration:_D/L_nomenclature|D/L designation]] defined by the stereochemistry at C5 in hexopyranoses <cite>McNaught1997</cite>. In addition to β-xylosidase activity, the equatorial blond cleaving β-glucosidase, β-galactosidase, and xylanase activities have been identified in one family GH39 enzyme <cite>Morrison2016</cite>. Furthermore, recent studies have characterized a GH39 from ''Pseudomonas aeruginosa'' active on the exopolysaccharide Psl (composed of D-mannose, D-glucose, and L-rhamnose) <cite>Baker2015 Byrd2009</cite>, and a group of fungal GH39 enzymes which possess α-L-(β-1,2)-arabinobiosidase activity and can release D-galactose-(α-1,2)-L-arabinose from arabinoxylans <cite>Jones2017</cite>. Enzymes from this family are currently found in bacteria and eukaryotes, although eleven gene sequences encoding putative Family GH39 enzymes from archaea have been reported in the CAZy database. The known β-xylosidase enzymes for which an enzyme activity has been experimentally established all come from microbes, while the α-iduronidase enzymes all come from metazoan eukaryotes. Additionally, while there is a reasonable degree of sequence similarity within the bacterial β-xylosidases in GH39 and within the α-iduronidases in GH39 <cite>Vocadlo1998</cite>, there is a much lower degree of homology between enzymes with differing activities <cite>Vocadlo1998 Baker2015 Jones2017 Ali-Ahmad2017</cite>. The best-studied enzymes are human α-iduronidase, whose deficiency causes Mucopolysaccharidosis I (also known as Hurler-Scheie syndrome), and the β-xylosidase from ''Thermoanaerobacterium saccharolyticum''.

==Kinetics and Mechanism==
Family GH39 enzymes are [[retaining]] [[glycoside hydrolases]] that follow the classical [[Koshland double-displacement mechanism]]. This has been demonstrated experimentally through NMR analysis of the first-formed sugar product produced by glycoside hydrolysis by the β-xylosidase from ''Thermoanaerobacterium saccharolyticum'' <cite>Armand1996</cite> and human α-iduronidase <cite>Nieman2003</cite>, and by covalent trapping of the [[catalytic nucleophile]] (described below) for these two enzymes <cite>Vocadlo1998 Nieman2003</cite>. These enzymes do not appear to require any activator or cofactor for activity.

==Catalytic Residues==
The [[catalytic nucleophile]] was first identified in the β-xylosidase from ''Thermoanaerobacterium saccharolyticum'' as Glu-277 in the sequence IILNSHFPNLPFHIT<u>'''E'''</u>Y by trapping of the 2-deoxy-2-fluoro-xylosyl-enzyme [[intermediate]] and subsequent peptide mapping by LC/MS-MS <cite>Vocadlo1998</cite>. A similar analysis performed on human α-iduronidase also successfully trapped the [[catalytic nucleophile]] and identified it as Glu-299 in the sequence IYND<u>'''E'''</u>AD <cite>Nieman2003</cite>, which confirmed previous theoretical predictions <cite>Durnad1997</cite>. The [[general acid/base]] residue has been experimentally identified in the β-xylosidase from ''Thermoanaerobacterium saccharolyticum'' as Glu-160 through trapping using the affinity label N-bromoacetyl-β-D-xylopyranosylamine and analysis of variant proteins created by mutation of that site <cite>Vocadlo2002</cite>.

==Three-dimensional structures==
The three-dimensional structure of the β-xylosidase from ''Thermoanaerobacterium saccharolyticum'' was first solved in 2004 <cite>Yang2004</cite>. Since then, the three dimensional structures for GH39 enzymes from ''Geobacillus stearothermophilus'' <cite>Czjzek2005 Czjzek2004</cite>, ''Homo sapiens'' <cite>Maita2013 Bie2013</cite>, ''Pseudomonas aeruginosa'' <cite>Baker2015</cite>, ''Neocallimastix frontalis'' <cite>Jones2017</cite>, and ''Bacteroides cellulosilyticus'' <cite>Ali-Ahmad2017</cite> have also been solved. GH39 enzymes are members of the [[Sequence-based classification of glycoside hydrolases|clan]] GH-A fold, consistent with the classic (α/β)<sub>8</sub> TIM barrel fold with the two key active site glutamic acids located at the C-terminal ends of β-strands 4 (acid/base) and 7 (nucleophile).

==Family Firsts==

;'''First stereochemistry determination'''
:''Thermoanaerobacterium saccharolyticum'' β-xylosidase by NMR <cite>Armand1996</cite>

;'''First [[catalytic nucleophile]] identification'''
:''Thermoanaerobacterium saccharolyticum'' β-xylosidase by 2-fluoroxylose labelling <cite>Nieman2003</cite>

;'''First [[general acid/base]] residue identification'''
:''Thermoanaerobacterium saccharolyticum'' β-xylosidase through labelling with N-bromoacetyl-β-D-xylopyranosylamine and kinetic analysis of mutants generated at the identified position <cite>Durnad1997</cite>

;'''First 3-D structure of a GH39 enzyme'''
:''Thermoanaerobacterium saccharolyticum'' β-xylosidase <cite>Vocadlo2002</cite>

==References==
<biblio>
#McNaught1997 pmid=9042704
#Vocadlo1998 pmid=9761746
#Armand1996 pmid=8612648
#Nieman2003 pmid=12834357
#Durnad1997 pmid=9134434
#Vocadlo2002 pmid=12146939
#Yang2004 pmid=14659747
#Czjzek2005 pmid=16212978
#Czjzek2004 pmid=14993701
#Morrison2016 pmid=27547582
#Baker2015 pmid=26424791
#Byrd2009 pmid=19659934
#Jones2017 pmid=28588026
#Ali-Ahmad2017 pmid=27890857
#Maita2013 pmid=23959878
##Bie2013 pmid=24036510

</biblio>

[[Category:Glycoside Hydrolase Families|GH039]]

Glycoside Hydrolase Family 39

2017-12-13T05:34:51Z

Darryl Jones:

{{CuratorApproved}}

* [[Author]]: ^^^Brian Rempel^^^, ^^^Darryl Jones^^^
* [[Responsible Curator]]: ^^^Steve Withers^^^

----

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family 39'''
|-
|'''Clan'''
|GH-A
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH39.html
|}
</div>

==Substrate Specificities==
This [[glycoside hydrolase]] family predominantly consists of two known enzyme activities: β-xylosidase and α-L-iduronidase. Both enzyme activities cleave equatorial glycosidic bonds: the 'α' designation of α-iduronidase is a consequence of the stereochemical designations used for carbohydrates in which the α/β designation is related to the [[Absolute_configuration:_D/L_nomenclature|D/L designation]] defined by the stereochemistry at C5 in hexopyranoses <cite>#1</cite>. In addition to β-xylosidase activity, the equatorial blond cleaving β-glucosidase, β-galactosidase, and xylanase activities have been identified in one family GH39 enzyme <cite>#11</cite>. Furthermore, recent studies have characterized a GH39 from ''Pseudomonas aeruginosa'' active on the exopolysaccharide Psl (composed of D-mannose, D-glucose, and L-rhamnose) <cite>#12 #13</cite>, and a group of fungal GH39 enzymes which possess α-L-(β-1,2)-arabinobiosidase activity and can release D-galactose-(α-1,2)-L-arabinose from arabinoxylans <cite>#14</cite>. Enzymes from this family are currently found in bacteria and eukaryotes, although eleven gene sequences encoding putative Family GH39 enzymes from archaea have been reported in the CAZy database. The known β-xylosidase enzymes for which an enzyme activity has been experimentally established all come from microbes, while the α-iduronidase enzymes all come from metazoan eukaryotes. Additionally, while there is a reasonable degree of sequence similarity within the bacterial β-xylosidases in GH39 and within the α-iduronidases in GH39 <cite>#2</cite>, there is a much lower degree of homology between enzymes with differing activities <cite>#2 #12 #14 #15</cite>. The best-studied enzymes are human α-iduronidase, whose deficiency causes Mucopolysaccharidosis I (also known as Hurler-Scheie syndrome), and the β-xylosidase from ''Thermoanaerobacterium saccharolyticum''.

==Kinetics and Mechanism==
Family GH39 enzymes are [[retaining]] [[glycoside hydrolases]] that follow the classical [[Koshland double-displacement mechanism]]. This has been demonstrated experimentally through NMR analysis of the first-formed sugar product produced by glycoside hydrolysis by the β-xylosidase from ''Thermoanaerobacterium saccharolyticum'' <cite>#3</cite> and human α-iduronidase <cite>#4</cite>, and by covalent trapping of the [[catalytic nucleophile]] (described below) for these two enzymes <cite>#2 #4</cite>. These enzymes do not appear to require any activator or cofactor for activity.

==Catalytic Residues==
The [[catalytic nucleophile]] was first identified in the β-xylosidase from ''Thermoanaerobacterium saccharolyticum'' as Glu-277 in the sequence IILNSHFPNLPFHIT<u>'''E'''</u>Y by trapping of the 2-deoxy-2-fluoro-xylosyl-enzyme [[intermediate]] and subsequent peptide mapping by LC/MS-MS <cite>#2</cite>. A similar analysis performed on human α-iduronidase also successfully trapped the [[catalytic nucleophile]] and identified it as Glu-299 in the sequence IYND<u>'''E'''</u>AD <cite>#4</cite>, which confirmed previous theoretical predictions <cite>#5</cite>. The [[general acid/base]] residue has been experimentally identified in the β-xylosidase from ''Thermoanaerobacterium saccharolyticum'' as Glu-160 through trapping using the affinity label N-bromoacetyl-β-D-xylopyranosylamine and analysis of variant proteins created by mutation of that site <cite>#6</cite>.

==Three-dimensional structures==
The three-dimensional structure of the β-xylosidase from ''Thermoanaerobacterium saccharolyticum'' was first solved in 2004 <cite>#7</cite>. Since then, the three dimensional structures for GH39 enzymes from ''Geobacillus stearothermophilus'' <cite>#8 #9</cite>, ''Homo sapiens'' <cite>#16 #17</cite>, ''Pseudomonas aeruginosa'' <cite>#12</cite>, ''Neocallimastix frontalis'' <cite>#14</cite>, and ''Bacteroides cellulosilyticus'' <cite>#15</cite> have also been solved. GH39 enzymes are members of the [[Sequence-based classification of glycoside hydrolases|clan]] GH-A fold, consistent with the classic (α/β)<sub>8</sub> TIM barrel fold with the two key active site glutamic acids located at the C-terminal ends of β-strands 4 (acid/base) and 7 (nucleophile).

==Family Firsts==

;'''First stereochemistry determination'''
:''Thermoanaerobacterium saccharolyticum'' β-xylosidase by NMR <cite>#3</cite>

;'''First [[catalytic nucleophile]] identification'''
:''Thermoanaerobacterium saccharolyticum'' β-xylosidase by 2-fluoroxylose labelling <cite>#4</cite>

;'''First [[general acid/base]] residue identification'''
:''Thermoanaerobacterium saccharolyticum'' β-xylosidase through labelling with N-bromoacetyl-β-D-xylopyranosylamine and kinetic analysis of mutants generated at the identified position <cite>#5</cite>

;'''First 3-D structure of a GH39 enzyme'''
:''Thermoanaerobacterium saccharolyticum'' β-xylosidase <cite>#6</cite>

==References==
<biblio>
#1 pmid=9042704
#2 pmid=9761746
#3 pmid=8612648
#4 pmid=12834357
#5 pmid=9134434
#6 pmid=12146939
#7 pmid=14659747
#8 pmid=16212978
#9 pmid=14993701
#10 pmid=15862278
#11 pmid=27547582
#12 pmid=26424791
#13 pmid=19659934
#14 pmid=28588026
#15 pmid=27890857
#16 pmid=23959878
#17 pmid=24036510

</biblio>

[[Category:Glycoside Hydrolase Families|GH039]]

Glycoside Hydrolase Family 39

2017-12-13T01:28:32Z

Darryl Jones:

{{CuratorApproved}}

* [[Author]]: ^^^Brian Rempel^^^, ^^^Darryl Jones^^^
* [[Responsible Curator]]: ^^^Steve Withers^^^

----

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family 39'''
|-
|'''Clan'''
|GH-A
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH39.html
|}
</div>

==Substrate Specificities==
This [[glycoside hydrolase]] family predominantly consists of two known enzyme activities: β-xylosidase and α-L-iduronidase. Both enzyme activities cleave equatorial glycosidic bonds: the 'α' designation of α-iduronidase is a consequence of the stereochemical designations used for carbohydrates in which the α/β designation is related to the [[Absolute_configuration:_D/L_nomenclature|D/L designation]] defined by the stereochemistry at C5 in hexopyranoses <cite>#1</cite>. In addition to β-xylosidase activity, the equatorial blond cleaving β-glucosidase, β-galactosidase, and xylanase activities have been identified in one family GH39 enzyme <cite>#11</cite>. Furthermore, recent studies have characterized a GH39 from ''Pseudomonas aeruginosa'' active on the exopolysaccharide Psl (composed of D-mannose, D-glucose, and L-rhamnose) <cite>#12 #13</cite>, and a group of fungal GH39 enzymes which posses α-L-(β-1,2)-arabinobiosidase activity and can release D-galactose-(α-1,2)-L-arabinose from arabinoxylans <cite>#14</cite>. Enzymes from this family are currently found in bacteria and eukaryotes, although eleven gene sequences encoding putative Family GH39 enzymes from archaea have been reported in the CAZy database. The known β-xylosidase enzymes for which an enzyme activity has been experimentally established all come from microbes, while the α-iduronidase enzymes all come from metazoan eukaryotes. Additionally, while there is a reasonable degree of sequence similarity within the bacterial β-xylosidases in GH39 and within the α-iduronidases in GH39 <cite>#2</cite>, there is a much lower degree of homology between enzymes with differing activities <cite>#2 #12 #14 #15</cite>. The best-studied enzymes are human α-iduronidase, whose deficiency causes Mucopolysaccharidosis I (also known as Hurler-Scheie syndrome), and the β-xylosidase from ''Thermoanaerobacterium saccharolyticum''.

==Kinetics and Mechanism==
Family GH39 enzymes are [[retaining]] [[glycoside hydrolases]] that follow the classical [[Koshland double-displacement mechanism]]. This has been demonstrated experimentally through NMR analysis of the first-formed sugar product produced by glycoside hydrolysis by the β-xylosidase from ''Thermoanaerobacterium saccharolyticum'' <cite>#3</cite> and human α-iduronidase <cite>#4</cite>, and by covalent trapping of the [[catalytic nucleophile]] (described below) for these two enzymes <cite>#2 #4</cite>. These enzymes do not appear to require any activator or cofactor for activity.

==Catalytic Residues==
The [[catalytic nucleophile]] was first identified in the β-xylosidase from ''Thermoanaerobacterium saccharolyticum'' as Glu-277 in the sequence IILNSHFPNLPFHIT<u>'''E'''</u>Y by trapping of the 2-deoxy-2-fluoro-xylosyl-enzyme [[intermediate]] and subsequent peptide mapping by LC/MS-MS <cite>#2</cite>. A similar analysis performed on human α-iduronidase also successfully trapped the [[catalytic nucleophile]] and identified it as Glu-299 in the sequence IYND<u>'''E'''</u>AD <cite>#4</cite>, which confirmed previous theoretical predictions <cite>#5</cite>. The [[general acid/base]] residue has been experimentally identified in the β-xylosidase from ''Thermoanaerobacterium saccharolyticum'' as Glu-160 through trapping using the affinity label N-bromoacetyl-β-D-xylopyranosylamine and analysis of variant proteins created by mutation of that site <cite>#6</cite>.

==Three-dimensional structures==
The three-dimensional structure of the β-xylosidase from ''Thermoanaerobacterium saccharolyticum'' was first solved in 2004 <cite>#7</cite>. Since then, the three dimensional structures for GH39 enzymes from ''Geobacillus stearothermophilus'' <cite>#8 #9</cite>, ''Homo sapiens'' <cite>#16 #17</cite>, ''Pseudomonas aeruginosa'' <cite>#12</cite>, ''Neocallimastix frontalis'' <cite>#14</cite>, and ''Bacteroides cellulosilyticus'' <cite>#15</cite> have also been solved. GH39 enzymes are members of the [[Sequence-based classification of glycoside hydrolases|clan]] GH-A fold, consistent with the classic (α/β)<sub>8</sub> TIM barrel fold with the two key active site glutamic acids located at the C-terminal ends of β-strands 4 (acid/base) and 7 (nucleophile).

==Family Firsts==

;'''First stereochemistry determination'''
:''Thermoanaerobacterium saccharolyticum'' β-xylosidase by NMR <cite>#3</cite>

;'''First [[catalytic nucleophile]] identification'''
:''Thermoanaerobacterium saccharolyticum'' β-xylosidase by 2-fluoroxylose labelling <cite>#4</cite>

;'''First [[general acid/base]] residue identification'''
:''Thermoanaerobacterium saccharolyticum'' β-xylosidase through labelling with N-bromoacetyl-β-D-xylopyranosylamine and kinetic analysis of mutants generated at the identified position <cite>#5</cite>

;'''First 3-D structure of a GH39 enzyme'''
:''Thermoanaerobacterium saccharolyticum'' β-xylosidase <cite>#6</cite>

==References==
<biblio>
#1 pmid=9042704
#2 pmid=9761746
#3 pmid=8612648
#4 pmid=12834357
#5 pmid=9134434
#6 pmid=12146939
#7 pmid=14659747
#8 pmid=16212978
#9 pmid=14993701
#10 pmid=15862278
#11 pmid=27547582
#12 pmid=26424791
#13 pmid=19659934
#14 pmid=28588026
#15 pmid=27890857
#16 pmid=23959878
#17 pmid=24036510

</biblio>

[[Category:Glycoside Hydrolase Families|GH039]]

User:Darryl Jones

2017-12-11T23:34:07Z

Darryl Jones:

[[Image:Blank_user-200px.png|200px|right]]
After completing graduate studies at the [https://uwaterloo.ca/ University of Waterloo] in the [https://uwaterloo.ca/biology/ Department of Biology], Darryl joined the group of Dr. ^^^ Wade Abbott^^^ at the [http://www.agr.gc.ca/index_e.php/ Agriculture and Agri-Food Canada][http://www.agr.gc.ca/eng/science-and-innovation/research-centres/alberta/lethbridge-research-and-development-centre/ Lethbridge Research and Development Centre]. As a member of Dr. Abbott's research team Darryl has been engaged in the identification and characterization of CAZymes from the intestinal microbiome, and the development of technologies involving carbohydrate modification for agricultural and intestinal health applications.

Darryl has contributed to studies of CAZymes from the following families:

'''Glycoside Hydrolases'''
*[[GH39]] from ''Neocallimastrix frontalis'' and ''Piromyces rhizinflatus'' <cite>Jones2017</cite>.

'''Polysaccharide Lyases'''
*[[PL2]] from ''Yersinia enterocolitica'' and ''Vibrio vulnificus'' <cite>McLean2015</cite>.

----
'''References'''
<biblio>
#McLean2015 pmid=26160170
#Jones2017 pmid=28588026
</biblio>


[[Category:Contributors|Jones,Darryl]]

User:Darryl Jones

2017-12-11T21:05:26Z

Darryl Jones:

[[Image:Blank_user-200px.png|200px|right]]
Darryl completed his graduate studies in the [https://uwaterloo.ca/biology/ Department of Biology] at the [https://uwaterloo.ca/ University of Waterloo], before joining the group of Dr. ^^^ Wade Abbott^^^ at the [http://www.agr.gc.ca/index_e.php/ Agriculture and Agri-Food Canada][http://www.agr.gc.ca/eng/science-and-innovation/research-centres/alberta/lethbridge-research-and-development-centre/ Lethbridge Research and Development Centre].

Darryl has contributed to studies of the following CAZyme Families:

'''Glycoside Hydrolases'''
*[[GH39]] from ''Neocallimastrix frontalis'' and ''Piromyces rhizinflatus'' <cite>Jones2017</cite>.

'''Polysaccharide Lyases'''
*[[PL2]] from ''Yersinia enterocolitica'' and ''Vibrio vulnificus'' <cite>McLean2015</cite>.

----
'''References'''
<biblio>
#McLean2015 pmid=26160170
#Jones2017 pmid=28588026
</biblio>


[[Category:Contributors|Jones,Darryl]]

User:Darryl Jones

2017-12-11T20:58:59Z

Darryl Jones:

[[Image:Blank_user-200px.png|200px|right]]
Darryl completed his graduate studies in the [https://uwaterloo.ca/biology/ Department of Biology] at the [https://uwaterloo.ca/ University of Waterloo], before joining the group of Dr. [[Wade Abbott]] at the [http://www.agr.gc.ca/index_e.php/ Agriculture and Agri-Food Canada][http://www.agr.gc.ca/eng/science-and-innovation/research-centres/alberta/lethbridge-research-centre/?id=1180547946064/ Lethbridge Research and Development Centre].

Darryl has contributed to studies of the following CAZyme Families:

'''Glycoside Hydrolases'''
*[[GH39]] from ''Neocallimastrix frontalis'' and ''Piromyces rhizinflatus'' <cite>Jones2017</cite>.

'''Polysaccharide Lyases'''
*[[PL2]] from ''Yersinia enterocolitica'' and ''Vibrio vulnificus'' <cite>McLean2015</cite>.

----
'''References'''
<biblio>
#McLean2015 pmid=26160170
#Jones2017 pmid=28588026
</biblio>


[[Category:Contributors|Jones,Darryl]]