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Difference between revisions of "Glycoside Hydrolase Family 117"
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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 bacteria ''Bacteroidetes plebeius'' (PDB: [{{PDBlink}}4ak5 4AK5]) <cite>Hehemann2012</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 bacteria ''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>. | 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>. | ||
− | 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>. | + | 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|Figure 3: Structure of the dimer of AghA. From <cite>Rebuffet2011</cite>.|600px|centre]] | [[Image:Agha_structure.png|thumb|Figure 3: Structure of the dimer of AghA. From <cite>Rebuffet2011</cite>.|600px|centre]] | ||
Revision as of 05:25, 25 June 2012
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- Author: ^^^Etienne Rebuffet^^^
- Responsible Curator: ^^^Mirjam Czjzek^^^
Glycoside Hydrolase Family GH117 | |
Clan | None |
Mechanism | Not known |
Active site residues | Not known |
CAZy DB link | |
http://www.cazy.org/GH117.html |
Substrate specificities
![](/images/thumb/9/9f/GH117_Phylogeny.png/400px-GH117_Phylogeny.png)
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 [1].
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 have 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.
![alt text](/images/d/d8/Gh117mechajan2012.jpg)
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 [1, 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 [1].
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) [1], the third one is from the human gut bacteria 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) [1]. 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 [2, 3]. 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 [1]. 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].
![](/images/thumb/c/c7/Agha_structure.png/600px-Agha_structure.png)
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 [1].
References
- 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 |
- 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 |
- 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 |