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Glycoside Hydrolase Family 117
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|Glycoside Hydrolase Family GH117|
|Active site residues||Not known|
|CAZy DB link|
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 .
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  (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 .
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 .
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) .
Three crystal structures of GH117 family have been reported. Two are enzymes from marine bacteria, one from Saccharophagus degradans (PDB: 3R4Y)  and one from Zobellia galactanivorans (PDB: 3P2N) , the third one is from the human gut bacterium Bacteroidetes plebeius (PDB: 4AK5) . 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) . 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 . 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 .
- 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 .
- Sugano Y, Kodama H, Terada I, Yamazaki Y, and Noma M. Purification and characterization of a novel enzyme, alpha-neoagarooligosaccharide hydrolase (alpha-NAOS hydrolase), from a marine bacterium, Vibrio sp. strain JT0107. J Bacteriol. 1994 Nov;176(22):6812-8.
- Suzuki H, Sawai Y, Suzuki T, and Kawai K. Purification and characterization of an extracellular alpha-neoagarooligosaccharide hydrolase from Bacillus sp. MK03. J Biosci Bioeng. 2002;93(5):456-63.
- Rebuffet E, Groisillier A, Thompson A, Jeudy A, Barbeyron T, Czjzek M, and Michel G. Discovery and structural characterization of a novel glycosidase family of marine origin. Environ Microbiol. 2011 May;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. Crystal structure of a key enzyme in the agarolytic pathway, α-neoagarobiose hydrolase from Saccharophagus degradans 2-40. Biochem Biophys Res Commun. 2011 Aug 26;412(2):238-44. DOI:10.1016/j.bbrc.2011.07.073 |
- Hehemann JH, Smyth L, Yadav A, Vocadlo DJ, and Boraston AB. Analysis of keystone enzyme in Agar hydrolysis provides insight into the degradation (of a polysaccharide from) red seaweeds. J Biol Chem. 2012 Apr 20;287(17):13985-95. DOI:10.1074/jbc.M112.345645 |
- Litzinger S, Fischer S, Polzer P, Diederichs K, Welte W, and Mayer C. Structural and kinetic analysis of Bacillus subtilis N-acetylglucosaminidase reveals a unique Asp-His dyad mechanism. J Biol Chem. 2010 Nov 12;285(46):35675-84. DOI:10.1074/jbc.M110.131037 |