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Difference between revisions of "Glycoside Hydrolase Family 117"
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− | * [[Author]]: | + | * [[Author]]: [[User:Etienne Rebuffet|Etienne Rebuffet]] |
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== Substrate specificities == | == 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 <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 | + | 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| | + | <br style="clear: both" /> |
− | + | 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 | ||
== Catalytic Residues == | == Catalytic Residues == | ||
− | From structural analysis and sequence alignments the catalytic residues have been predicted to be | + | 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 == | ||
− | + | 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>. | |
− | + | 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 | + | 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>.]] | ||
+ | <br style="clear: both" /> | ||
== Family Firsts == | == Family Firsts == | ||
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#Sugano1994 pmid=7961439 | #Sugano1994 pmid=7961439 | ||
#Suzuki2002 pmid=16233232 | #Suzuki2002 pmid=16233232 | ||
+ | #Litzinger2010 pmid=20826810 | ||
#Rebuffet2011 pmid=21332624 | #Rebuffet2011 pmid=21332624 | ||
− | # | + | #Ha2011 pmid=21810409 |
+ | #Hehemann2012 pmid=22393053 | ||
</biblio> | </biblio> | ||
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[[Category:Glycoside Hydrolase Families|GH117]] | [[Category:Glycoside Hydrolase Families|GH117]] |
Latest revision as of 13:14, 18 December 2021
This page has been approved by the Responsible Curator as essentially complete. CAZypedia is a living document, so further improvement of this page is still possible. If you would like to suggest an addition or correction, please contact the page's Responsible Curator directly by e-mail.
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].
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].
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].
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
- 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 |
- 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 |
- 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 |
- 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 |
- 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 |
- 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 |