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Glycoside Hydrolase Family 125
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- Author: ^^^Alisdair Boraston^^^
- Responsible Curator: ^^^Alisdair Boraston^^^
| Glycoside Hydrolase Family GH125 | |
| Clan | GH-L |
| Mechanism | inverting |
| Active site residues | known |
| CAZy DB link | |
| http://www.cazy.org/GH125.html | |
Substrate specificities
The currently characterized family 125 glycoside hydrolyses, which include the examples from Streptococcus pneumoniae (SpGH125) and Clostridium perfringens (CpGH125), are α-mannosidases with specificity for α-1,6-linked non-reducing terminal mannose residues [1].
Kinetics and Mechanism
Kinetic characterization of 2,4-dinitrophenyl α-D-mannopyranoside hydrolysis by SpGH125 and Cp125 revealed that this is a poor substrate for these enzymes. Monitoring the hydrolysis of methyl 6-O-(α-D-mannopyranosyl)-β-D-mannopyranoside by sup>1H NMR spectroscopy revealed that CpGH125 and SpGH125 act with inversion of stereochemistry. The structural analysis of both enzymes reveal an arrangement of catalytic residues that is consistent with this mechanistic assignment [1].
Catalytic Residues
The structural analysis of CpGH125 suggests it uses aspartate 220 as a catalytic acid and glutamate 393 as catalytic base. The corresponding residues in SpGH125 are aspartame 218 and glutamate 391.
Three-dimensional structures
The three dimensional structures of CpGH125 (3qt3, 3qt9, and 2nvp), SpGH125 (3qpf, 3qry, and 3qsp) are available and reveal both the (α/α)6-fold of the family as well the details of inhibitor and substrate recognition. Thought the proteins are uncharacterized structures are also available for two GH125 enzymes from BActeroides ovatus (3on6, and 3p2c) and on GH125 from Bacteroides thetaiotaomicron (2pov).
Family Firsts
- First stereochemistry determination
- 1H NMR spectroscopy revealed that CpGH125 and SpGH125 act with inversion of stereochemistry [1].
- First catalytic nucleophile identification
- Cite some reference here, with a short (1-2 sentence) explanation [2].
- First general acid/base residue identification
- Cite some reference here, with a short (1-2 sentence) explanation [3].
- First 3-D structure
- Cite some reference here, with a short (1-2 sentence) explanation [4].
References
- Gregg KJ, Zandberg WF, Hehemann JH, Whitworth GE, Deng L, Vocadlo DJ, and Boraston AB. (2011). Analysis of a new family of widely distributed metal-independent alpha-mannosidases provides unique insight into the processing of N-linked glycans. J Biol Chem. 2011;286(17):15586-96. DOI:10.1074/jbc.M111.223172 |