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- Title
Structure and mechanism of a bacterial β-glucosaminidase having O-GlcNAcase activity.
- Authors
Dennis, Rebecca J; Taylor, Edward J; Macauley, Matthew S; Stubbs, Keith A; Turkenburg, Johan P; Hart, Samuel J; Black, Gary N; Vocadlo, David J; Davies, Gideon J
- Abstract
O-GlcNAc is an abundant post-translational modification of serine and threonine residues of nucleocytoplasmic proteins. This modification, found only within higher eukaryotes, is a dynamic modification that is often reciprocal to phosphorylation. In a manner analogous to phosphatases, a glycoside hydrolase termed O-GlcNAcase cleaves O-GlcNAc from modified proteins. Enzymes with high sequence similarity to human O-GlcNAcase are also found in human pathogens and symbionts. We report the three-dimensional structure of O-GlcNAcase from the human gut symbiont Bacteroides thetaiotaomicron both in its native form and in complex with a mimic of the reaction intermediate. Mutagenesis and kinetics studies show that the bacterial enzyme, very similarly to its human counterpart, operates via an unusual 'substrate-assisted' catalytic mechanism, which will inform the rational design of enzyme inhibitors.
- Subjects
PROTEINS; PHOSPHORYLATION; PHOSPHATASES; GLYCOSIDASES; ENZYMES
- Publication
Nature Structural & Molecular Biology, 2006, Vol 13, Issue 4, p365
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb1079