Glycoside Hydrolase Family 92

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• Author: ^^^Harry Gilbert^^^
• Responsible Curator: ^^^Harry Gilbert^^^

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Glycoside Hydrolase Family GHnn
Clan	GH-x
Mechanism	retaining/inverting
Active site residues	known/not known
CAZy DB link
http://www.cazy.org/fam/GHnn.html

Substrate specificities

GH92 enzymes are exo-acting alpha-mannosidases. The first reported enzyme activity from this family was an alpha1,2-mannosidase from Microbacterium sp. M-90. [1] Recently the characterization of 22 GH92 enzymes from Bacteroides thetaiotaomicron confirmed an exo-mode of action but alpha1,2-mannosidase, alpha1,3-mannosidase, alpha1,4-mannosidase and alpha1,6-mannosidase activities were detected [2] [3, 4, 5].

Kinetics and Mechanism

1H-NMR studies on three GH92s that displayed alpha1,2-, alpha1,3- and alpha1,4-mannosidase activities all generated beta-mannose indicating that these enzymes catalyse glycosidic bond hydrolysis through a single displacement mechanism leading to inversion of anomeric configuration [3, 4, 5]. GH92 enzymes are calcium-dependent alpha-mannosidases. The requirement for the metal ion is restricted to only three GH92 families all of which are exo-alpha mannosidases. Mechanistically this may indicated that the lack of distorting binding energy provided by the -2 or +1 subsites imposes a requirement for conformational flexibility at the -1 subsite (recognition of the ground state and the transition state conformations), which is best achieved by a metal ion interaction with O2 and O3. Three inhibitors bound to the alpha1,2-mannosidase Bt3990 in approximate 1S5/B2,5 and 1,4B/1S5 conformations indicating that catalysis is mediated by a Boat2,5 transition state.

Catalytic Residues

Content is to be added here. Based on 3D structural data on the alpha1,2-mannosidase Bt3990 Glu533 is the predicted catalytic acid. This view is supported by a mutant of this residue, which is essentially inactive, and its conservation throughout the GH92 family.

Three-dimensional structures

Content is to be added here.

Family Firsts

First sterochemistry determination

Cite some reference here, with a short (1-2 sentence) explanation [6].

First catalytic nucleophile identification

Cite some reference here, with a short (1-2 sentence) explanation [7].

First general acid/base residue identification

Cite some reference here, with a short (1-2 sentence) explanation [8].

First 3-D structure

Cite some reference here, with a short (1-2 sentence) explanation [9].

References

3. et al (2009) Nature Chemical Biology

6. Comfort DA, Bobrov KS, Ivanen DR, Shabalin KA, Harris JM, Kulminskaya AA, Brumer H, and Kelly RM. (2007). Biochemical analysis of Thermotoga maritima GH36 alpha-galactosidase (TmGalA) confirms the mechanistic commonality of clan GH-D glycoside hydrolases. Biochemistry. 2007;46(11):3319-30. DOI:10.1021/bi061521n |
8. He S and Withers SG. (1997). Assignment of sweet almond beta-glucosidase as a family 1 glycosidase and identification of its active site nucleophile. J Biol Chem. 1997;272(40):24864-7. DOI:10.1074/jbc.272.40.24864 |
9. Robert V. Stick and Spencer J. Williams. (2009) Carbohydrates. Elsevier Science.