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Structure and mechanism of a bacterial ß-glucosaminidase having O-GlcNAcase activity

Dennis, R.J., Taylor, E.J., Macauley, M.S., Stubbs, K.A., Turkenburg, J.P., Hart, S.J., Black, G.N., Vocadlo, D.J. and Davies, G.J. (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

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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.

Item Type: Article
Institution: The University of York
Academic Units: The University of 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
URI: http://eprints.whiterose.ac.uk/id/eprint/7647

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