BACTEROIDES THETAIOTAOMICRON HEXOSAMINIDASE WITH O-GLCNACASE ACTIVITY

File:2cho.gif


2cho, resolution 1.85Å

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OverviewOverview

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.

About this StructureAbout this Structure

2CHO is a Single protein structure of sequence from Bacteroides thetaiotaomicron with , and as ligands. Active as Beta-N-acetylhexosaminidase, with EC number 3.2.1.52 Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

Structure and mechanism of a bacterial beta-glucosaminidase having O-GlcNAcase activity., Dennis RJ, Taylor EJ, Macauley MS, Stubbs KA, Turkenburg JP, Hart SJ, Black GN, Vocadlo DJ, Davies GJ, Nat Struct Mol Biol. 2006 Apr;13(4):365-71. Epub 2006 Mar 26. PMID:16565725

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