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 1545-9993Full text not available from this repository.
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.
|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|
|Publisher:||Nature Publishing Group|