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Chem Biol. 2008 Oct 20;15(10):1058-67. doi: 10.1016/j.chembiol.2008.09.005. Epub 2008 Oct 9.

Divergence of catalytic mechanism within a glycosidase family provides insight into evolution of carbohydrate metabolism by human gut flora.

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  • 1York Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York, YO10 5YW, UK. gloster@ysbl.york.ac.uk

Abstract

Enzymatic cleavage of the glycosidic bond yields products in which the anomeric configuration is either retained or inverted. Each mechanism reflects the dispositions of the enzyme functional groups; a facet of which is essentially conserved in 113 glycoside hydrolase (GH) families. We show that family GH97 has diverged significantly, as it contains both inverting and retaining alpha-glycosidases. This reflects evolution of the active center; a glutamate acts as a general base in inverting members, exemplified by Bacteroides thetaiotaomicron alpha-glucosidase BtGH97a, whereas an aspartate likely acts as a nucleophile in retaining members. The structure of BtGH97a and its complexes with inhibitors, coupled to kinetic analysis of active-site variants, reveals an unusual calcium ion dependence. 1H NMR analysis shows an inversion mechanism for BtGH97a, whereas another GH97 enzyme from B. thetaiotaomicron, BtGH97b, functions as a retaining alpha-galactosidase.

PMID:
18848471
PMCID:
PMC2670981
DOI:
10.1016/j.chembiol.2008.09.005
[PubMed - indexed for MEDLINE]
Free PMC Article
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