2CHO

Bacteroides thetaiotaomicron hexosaminidase with O-GlcNAcase activity

Summary for 2CHO

• Entry DOI: 10.2210/pdb2cho/pdb
• Related: 2CHN
• Descriptor: GLUCOSAMINIDASE, CALCIUM ION, ACETATE ION, ... (6 entities in total)
• Functional Keywords: o-glcnacase, hydrolase, n-acetylglucosamine
• Biological source: BACTEROIDES THETAIOTAOMICRON; More
• Total number of polymer chains: 4
• Total formula weight: 167475.64

Authors

Dennis, R.J.,Taylor, E.J.,Macauley, M.S.,Stubbs, K.A.,Turkenburg, J.P.,Hart, S.J.,Black, G.N.,Vocadlo, D.J.,Davies, G.J. (deposition date: 2006-03-16, release date: 2006-06-19, Last modification date: 2024-05-08)

Primary citation

Dennis, R.J.,Taylor, E.J.,Macauley, M.S.,Stubbs, K.A.,Turkenburg, J.P.,Hart, S.J.,Black, G.N.,Vocadlo, D.J.,Davies, G.J.
Structure and Mechanism of a Bacterial B-Glucosaminidase Having O-Glcnacase Activity
Nat.Struct.Mol.Biol., 13:365-, 2006

PubMed 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.

PubMed: 16565725
DOI: 10.1038/NSMB1079

Experimental method

X-RAY DIFFRACTION (1.85 Å)