2CHN

Bacteroides thetaiotaomicron hexosaminidase with O-GlcNAcase activity- NAG-thiazoline complex

Summary for 2CHN

• Entry DOI: 10.2210/pdb2chn/pdb
• Related: 2CHO
• Descriptor: GLUCOSAMINIDASE, CALCIUM ION, 3AR,5R,6S,7R,7AR-5-HYDROXYMETHYL-2-METHYL-5,6,7,7A-TETRAHYDRO-3AH-PYRANO[3,2-D]THIAZOLE-6,7-DIOL, ... (6 entities in total)
• Functional Keywords: o-glcnacase, hydrolase, n-acetylglucosamibe
• Biological source: BACTEROIDES THETAIOTAOMICRON; More
• Total number of polymer chains: 4
• Total formula weight: 169126.53

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: 2006-03-15, release date: 2006-05-08, Last modification date: 2024-10-09)

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 (1.95 Å)