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Difference between revisions of "Glycoside Hydrolase Family 117"

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* [[Author]]: [[User:Etienne Rebuffet|Etienne Rebuffet]]
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== Substrate specificities ==
 
== Substrate specificities ==
[[Image:GH117_Phylogeny.png|thumb|Figure 1: Phylogeny of GH117 family. From <cite>Rebuffet2011</cite>.|400px|right]]
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The only activity so far characterized within this recently discovered family of [[glycoside hydrolases]] is that of α-1,3-L-(3,6-anhydro)-galactosidase <cite>Sugano1994 Suzuki2002 Rebuffet2011 Ha2011 Hehemann2012</cite>. Nevertheless phylogenetic analyses (Figure 1) of this family together with activity tests for another member, Zg3597 (Clade C), show that the family GH117 most probably is polyspecific
The only activity so far characterized within this recently discovered family of [[glycoside hydrolases]] is that of α-1,3-L-(3,6-anhydro)-galactosidase <cite>Sugano1994 Suzuki2002 Rebuffet2011 Hehemann2012</cite>. Nevertheless phylogenetic analyses (Figure 1) of this family together with activity tests for another member, Zg3597 (Clade C), show that the family GH117 most probably is polyspecific <cite>Rebuffet2011</cite>.
+
<cite>Rebuffet2011</cite>.
 +
[[Image:GH117_Phylogeny.png|thumb|left|150px|Figure 1: Phylogeny of GH117 family (''click to enlarge''). From <cite>Rebuffet2011</cite>.]]
 +
<br style="clear: both" />
  
 
== Kinetics and Mechanism ==
 
== Kinetics and Mechanism ==
The stereochemical outcome of members of glycoside hydrolase family GH117 is still not determined experimentally. Nevertheless a mechanism based on the structure of an inactive mutant complexed to a neoagarobiose have been proposed <cite>Hehemann2012</cite> (Figure 2). In this unusual inverting catalytic mechanism an aspartic acid acting as the base and a histidine acting as the acid.
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The stereochemical outcome of members of glycoside hydrolase family GH117 is still not determined experimentally. Nevertheless a mechanism based on the structure of an inactive mutant (''Bp''GH117 E303Q) complexed to a neoagarobiose has been proposed <cite>Hehemann2012</cite> (Figure 2). In this unusual inverting catalytic mechanism an aspartic acid acting as the base and a histidine acting as the acid. An analogous Asp-His dyad has been similarly reported to act as the general base catalyst in the retaining mechanism of select [[GH3]] members <cite>Litzinger2010</cite>.
 
+
[[File:gh117mechajan2012.jpg|thumb|left|800px|Figure 2: Proposed mechanism of α-1,3-L-(3,6-anhydro)-galactosidase. From <cite>Hehemann2012</cite>]]
[[File:gh117mechajan2012.jpg|800x200px|Proposed mechanism of α-1,3-L-(3,6-anhydro)-galactosidase. From <cite>Hehemann2012</cite>]]
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<br style="clear: both" />
 
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Two of the three 3D structures revealed the presence of a divalent cation, directly coordinated only by water molecules, close to the active site, which could activate the catalytic water molecule and provide the energy needed for the enzymatic reaction <cite>Rebuffet2011 Hehemann2012</cite>. Sequence alignments suggest that the enzymes of clades B and C do not bind divalent cation, which could be related to their difference in substrate specificity <cite>Rebuffet2011</cite>.
Two of the three 3D structures revealed the presence of a divalent cation, directly coordinated only by water molecules, close to the active site, which could activate the catalytic water molecule and provide the energy needed for the enzymatic reaction <cite>Rebuffet2011 Hehemann2012</cite>. Sequence alignments suggest that the enzymes of clades B and C do not bind zinc ions, which could be related to their difference in substrate specificity <cite>Rebuffet2011</cite>.
 
  
 
== Catalytic Residues ==
 
== Catalytic Residues ==
From structural analysis and sequence alignments the catalytic residues have been predicted to be two of the three acidic residues Asp-97, Asp-252 and Glu-310 (Zg4663 numbering) <cite>Rebuffet2011</cite>.
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From structural analysis and sequence alignments the catalytic residues have been predicted to be Asp-90 as the base and His-302 as the acid ''Bp''GH117 numbering) <cite>Hehemann2012</cite>.
  
 
== Three-dimensional structures ==
 
== Three-dimensional structures ==
At the moment two members of GH117 family have been crystallized. Both are enzymes from marine bacteria, one from ''Saccharophagus degradans'' <cite>Lee2009</cite> and one from ''Zobellia galactanivorans'' <cite>Rebuffet2011</cite>. A crystal structure has only been reported for the α-1,3-L-(3,6-anhydro)-galactosidase (AhgA, Zg4663) from ''Z. galactanivorans'' (PDB: [{{PDBlink}}3p2n 3p2n]) <cite>Rebuffet2011</cite>.
+
Three crystal structures of GH117 family have been reported. Two are enzymes from marine bacteria, one from ''Saccharophagus degradans'' (PDB: [{{PDBlink}}3r4y 3R4Y]) <cite>Ha2011</cite> and one from ''Zobellia galactanivorans'' (PDB: [{{PDBlink}}3p2n 3P2N]) <cite>Rebuffet2011</cite>, the third one is from the human gut bacterium ''Bacteroidetes plebeius'' (PDB: [{{PDBlink}}4ak5 4AK5]) <cite>Hehemann2012</cite>.
AhgA adopts a five-bladed β-propeller fold and forms a dimer via domain-swapping of the N-terminal HTH (Helix-Turn-Helix) domain (Figure 2) <cite>Rebuffet2011</cite>. Interestingly, previous sequences reported from ''Vibrio sp.'' JT0107 and ''Bacillus sp.'' MK03 contain the conserved domain-swapping signature SxAxxR in the HTH domain. Consistently, these proteins were reported to form multimers (a dimer and an octamer respectively), based on calibrated gel filtration estimations <cite>Sugano1994 Suzuki2002 </cite>. In contrast, RB13146 (Clade B) lacks the domain-swapping signature, in which the crucial residues are missing. This enzyme from ''R. baltica'' thus likely occurs as a monomer and may represent an ‘ancestral’ form of the GH117 family, which would be limited to the catalytic β-propeller domain <cite>Rebuffet2011</cite>.
+
GH117 adopts a five-bladed β-propeller fold and forms a dimer via domain-swapping of the N-terminal HTH (Helix-Turn-Helix) domain (Figure 3) <cite>Rebuffet2011</cite>. Interestingly, previous sequences reported from ''Vibrio sp.'' JT0107 and ''Bacillus sp.'' MK03 contain the conserved domain-swapping signature SxAxxR in the HTH domain. Consistently, these proteins were reported to form multimers (a dimer and an octamer respectively), based on calibrated gel filtration estimations <cite>Sugano1994 Suzuki2002 </cite>. In contrast, RB13146 (Clade B) lacks the domain-swapping signature, in which the crucial residues are missing. This enzyme from ''R. baltica'' thus likely occurs as a monomer and may represent an ‘ancestral’ form of the GH117 family, which would be limited to the catalytic β-propeller domain <cite>Rebuffet2011</cite>.
[[Image:Agha_structure.png|thumb|Figure 2: Structure of the dimer of AghA. From <cite>Rebuffet2011</cite>.|600px|centre]]
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Structure of ''Sd''NABH and ''Bp''GH117 possess a ordered C terminus part which also interact with the adjacent monomer <cite>Ha2011 Hehemann2012</cite>. Moreover in the case of ''Bp''GH117, His-392 from the C terminus of the monomer A participate in the substrate binding in the binding pocket of monomer B, and aims versa <cite>Hehemann2012</cite>.  
 +
[[Image:Agha_structure.png|thumb|left|600px|Figure 3: Structure of the dimer of AghA. From <cite>Rebuffet2011</cite>.]]
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<br style="clear: both" />
  
 
== Family Firsts ==
 
== Family Firsts ==
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#Sugano1994 pmid=7961439
 
#Sugano1994 pmid=7961439
 
#Suzuki2002 pmid=16233232
 
#Suzuki2002 pmid=16233232
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#Litzinger2010 pmid=20826810
 
#Rebuffet2011 pmid=21332624
 
#Rebuffet2011 pmid=21332624
#Lee2009 pmid=20054134
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#Ha2011 pmid=21810409
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#Hehemann2012 pmid=22393053
 
</biblio>
 
</biblio>
 
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#Sinnott1990 Sinnott, M.L. (1990) Catalytic mechanisms of enzymic glycosyl transfer. Chem. Rev. 90, 1171-1202. [http://dx.doi.org/10.1021/cr00105a006 DOI: 10.1021/cr00105a006]
 
This is an example of how to make references to a journal article <cite>Comfort2007</cite>. (See the References section below).  Multiple references can go in the same place like this <cite>Comfort2007 He1999</cite>.  You can even cite books using just the ISBN <cite>StickWilliams</cite>.  References that are not in PubMed can be typed in by hand <cite>Sinnott1990</cite>. 
 
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[[Category:Glycoside Hydrolase Families|GH117]]
 
[[Category:Glycoside Hydrolase Families|GH117]]

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Glycoside Hydrolase Family GH117
Clan None
Mechanism Not known
Active site residues Not known
CAZy DB link
https://www.cazy.org/GH117.html


Substrate specificities

The only activity so far characterized within this recently discovered family of glycoside hydrolases is that of α-1,3-L-(3,6-anhydro)-galactosidase [1, 2, 3, 4, 5]. Nevertheless phylogenetic analyses (Figure 1) of this family together with activity tests for another member, Zg3597 (Clade C), show that the family GH117 most probably is polyspecific [3].

Figure 1: Phylogeny of GH117 family (click to enlarge). From [3].


Kinetics and Mechanism

The stereochemical outcome of members of glycoside hydrolase family GH117 is still not determined experimentally. Nevertheless a mechanism based on the structure of an inactive mutant (BpGH117 E303Q) complexed to a neoagarobiose has been proposed [5] (Figure 2). In this unusual inverting catalytic mechanism an aspartic acid acting as the base and a histidine acting as the acid. An analogous Asp-His dyad has been similarly reported to act as the general base catalyst in the retaining mechanism of select GH3 members [6].

Figure 2: Proposed mechanism of α-1,3-L-(3,6-anhydro)-galactosidase. From [5]


Two of the three 3D structures revealed the presence of a divalent cation, directly coordinated only by water molecules, close to the active site, which could activate the catalytic water molecule and provide the energy needed for the enzymatic reaction [3, 5]. Sequence alignments suggest that the enzymes of clades B and C do not bind divalent cation, which could be related to their difference in substrate specificity [3].

Catalytic Residues

From structural analysis and sequence alignments the catalytic residues have been predicted to be Asp-90 as the base and His-302 as the acid BpGH117 numbering) [5].

Three-dimensional structures

Three crystal structures of GH117 family have been reported. Two are enzymes from marine bacteria, one from Saccharophagus degradans (PDB: 3R4Y) [4] and one from Zobellia galactanivorans (PDB: 3P2N) [3], the third one is from the human gut bacterium Bacteroidetes plebeius (PDB: 4AK5) [5]. GH117 adopts a five-bladed β-propeller fold and forms a dimer via domain-swapping of the N-terminal HTH (Helix-Turn-Helix) domain (Figure 3) [3]. Interestingly, previous sequences reported from Vibrio sp. JT0107 and Bacillus sp. MK03 contain the conserved domain-swapping signature SxAxxR in the HTH domain. Consistently, these proteins were reported to form multimers (a dimer and an octamer respectively), based on calibrated gel filtration estimations [1, 2]. In contrast, RB13146 (Clade B) lacks the domain-swapping signature, in which the crucial residues are missing. This enzyme from R. baltica thus likely occurs as a monomer and may represent an ‘ancestral’ form of the GH117 family, which would be limited to the catalytic β-propeller domain [3]. Structure of SdNABH and BpGH117 possess a ordered C terminus part which also interact with the adjacent monomer [4, 5]. Moreover in the case of BpGH117, His-392 from the C terminus of the monomer A participate in the substrate binding in the binding pocket of monomer B, and aims versa [5].

Figure 3: Structure of the dimer of AghA. From [3].


Family Firsts

First stereochemistry determination
not determined yet.
First catalytic nucleophile identification
not determined yet.
First general acid/base residue identification
not determined yet.
First 3-D structure
The first 3D structure was reported in 2011 for an α-1,3-L-(3,6-anhydro)-galactosidase (AhgA or Zg4663) from the marine bacteria Zobellia galactanivorans, PDB: 3p2n [3].

References

  1. Sugano Y, Kodama H, Terada I, Yamazaki Y, and Noma M. (1994). Purification and characterization of a novel enzyme, alpha-neoagarooligosaccharide hydrolase (alpha-NAOS hydrolase), from a marine bacterium, Vibrio sp. strain JT0107. J Bacteriol. 1994;176(22):6812-8. DOI:10.1128/jb.176.22.6812-6818.1994 | PubMed ID:7961439 [Sugano1994]
  2. Suzuki H, Sawai Y, Suzuki T, and Kawai K. (2002). Purification and characterization of an extracellular alpha-neoagarooligosaccharide hydrolase from Bacillus sp. MK03. J Biosci Bioeng. 2002;93(5):456-63. DOI:10.1016/s1389-1723(02)80092-5 | PubMed ID:16233232 [Suzuki2002]
  3. Rebuffet E, Groisillier A, Thompson A, Jeudy A, Barbeyron T, Czjzek M, and Michel G. (2011). Discovery and structural characterization of a novel glycosidase family of marine origin. Environ Microbiol. 2011;13(5):1253-70. DOI:10.1111/j.1462-2920.2011.02426.x | PubMed ID:21332624 [Rebuffet2011]
  4. Ha SC, Lee S, Lee J, Kim HT, Ko HJ, Kim KH, and Choi IG. (2011). Crystal structure of a key enzyme in the agarolytic pathway, α-neoagarobiose hydrolase from Saccharophagus degradans 2-40. Biochem Biophys Res Commun. 2011;412(2):238-44. DOI:10.1016/j.bbrc.2011.07.073 | PubMed ID:21810409 [Ha2011]
  5. Hehemann JH, Smyth L, Yadav A, Vocadlo DJ, and Boraston AB. (2012). Analysis of keystone enzyme in Agar hydrolysis provides insight into the degradation (of a polysaccharide from) red seaweeds. J Biol Chem. 2012;287(17):13985-95. DOI:10.1074/jbc.M112.345645 | PubMed ID:22393053 [Hehemann2012]
  6. Litzinger S, Fischer S, Polzer P, Diederichs K, Welte W, and Mayer C. (2010). Structural and kinetic analysis of Bacillus subtilis N-acetylglucosaminidase reveals a unique Asp-His dyad mechanism. J Biol Chem. 2010;285(46):35675-84. DOI:10.1074/jbc.M110.131037 | PubMed ID:20826810 [Litzinger2010]

All Medline abstracts: PubMed