2wyx

Neutron structure of a class A Beta-lactamase Toho-1 E166A R274N R276N triple mutant

spinqualitylabelsall models 2wyx, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2wyx is a 1 chain structure with sequence from Escherichia coli BL21. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Neutron Diffraction, Resolution 2.1Å Ligands: DOD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BLT1_ECOLX Has strong cefotaxime-hydrolyzing activity. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed beta-Lactam antibiotics have been used effectively over several decades against many types of bacterial infectious diseases. However, the most common cause of resistance to the beta-lactam antibiotics is the production of beta-lactamase enzymes that inactivate beta-lactams by rapidly hydrolyzing the amide group of the beta-lactam ring. Specifically, the class A extended-spectrum beta-lactamases (ESBLs) and inhibitor-resistant enzymes arose that were capable of hydrolyzing penicillins and the expanded-spectrum cephalosporins and monobactams in resistant bacteria, which lead to treatment problems in many clinical settings. A more complete understanding of the mechanism of catalysis of these ESBL enzymes will impact current antibiotic drug discovery efforts. Here, we describe the neutron structure of the class A, CTX-M-type ESBL Toho-1 E166A/R274N/R276N triple mutant in its apo form, which is the first reported neutron structure of a beta-lactamase enzyme. This neutron structure clearly reveals the active-site protonation states and hydrogen-bonding network of the apo Toho-1 ESBL prior to substrate binding and subsequent acylation. The protonation states of the active-site residues Ser70, Lys73, Ser130, and Lys234 in this neutron structure are consistent with the prediction of a proton transfer pathway from Lys73 to Ser130 that is likely dependent on the conformation of Lys73, which has been hypothesized to be coupled to the protonation state of Glu166 during the acylation reaction. Thus, this neutron structure is in agreement with a proposed mechanism for acylation that identifies Glu166 as the general base for catalysis. Neutron diffraction studies of a class A beta-lactamase Toho-1 E166A/R274N/R276N triple mutant.,Tomanicek SJ, Blakeley MP, Cooper J, Chen Y, Afonine PV, Coates L J Mol Biol. 2010 Mar 5;396(4):1070-80. Epub 2009 Dec 28. PMID:20036259 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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