2xm2

BTGH84 IN COMPLEX WITH LOGNAC

spinqualitylabelsall models 2xm2, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xm2 is a 2 chain structure with sequence from Bacteroides thetaiotaomicron vpi-5482. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, LOG Related: 2vvn, 2wzh, 2w67, 2wca, 2vvs, 2j4g, 2w4x, 2xm1, 2cho, 2xj7, 2jiw, 2chn, 2x0h, 2wzi, 2j47, 2w66 Activity: Beta-N-acetylhexosaminidase, with EC number 3.2.1.52 Resources: FirstGlance, OCA, RCSB, PDBsum Function [OGA_BACTN] Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins. Publication Abstract from PubMed The dynamic, intracellular, O-GlcNAc modification is of continuing interest and one whose study through targeted "chemical genetics" approaches is set to increase. Of particular importance is the inhibition of the O-GlcNAc hydrolase, O-GlcNAcase (OGA), since this provides a route to elevate cellular O-GlcNAc levels, and subsequent phenotypic evaluation. Such a small molecule approach complements other methods and potentially avoids changes in protein-protein interactions that manifest themselves in molecular biological approaches to O-GlcNAc transferase knockout or over-expression. Here we describe the kinetic, thermodynamic and three-dimensional structural analysis of a bacterial OGA analogue from Bacteroides thetaiotaomicron, BtGH84, in complex with a lactone oxime (LOGNAc) and a lactam form of N-acetylglucosamine and compare their binding signatures with that of the more potent inhibitor O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc). We show that both LOGNAc and the N-acetyl gluconolactam are significantly poorer inhibitors than PUGNAc, which may reflect poorer mimicry of transition state geometry and steric clashes with the enzyme upon binding; drawbacks that the phenyl carbamate adornment of PUGNAc helps mitigate. Implications for the design of future generations of inhibitors are discussed. Inhibition of a bacterial O-GlcNAcase homologue by lactone and lactam derivatives: structural, kinetic and thermodynamic analyses.,He Y, Bubb AK, Stubbs KA, Gloster TM, Davies GJ Amino Acids. 2011 Mar;40(3):829-39. Epub 2010 Aug 6. PMID:20689974 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-Hexosaminidase

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