Dennis, R.J., Taylor, E.J., Macauley, M.S. et al. (6 more authors) (2006) Structure and mechanism of a bacterial ß-glucosaminidase having O-GlcNAcase activity. Nature Structural & Molecular Biology, 13 (13). pp. 365-371. ISSN 1545-9993
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | York RAE Import |
Date Deposited: | 09 Feb 2009 10:18 |
Last Modified: | 09 Feb 2009 10:20 |
Published Version: | http://dx.doi.org/10.1038/nsmb1079 |
Status: | Published |
Publisher: | Nature Publishing Group |
Identification Number: | 10.1038/nsmb1079 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:7647 |