5a92

15K X-ray structure with Cefotaxime: Exploring the Mechanism of beta- Lactam Ring Protonation in the Class A beta-lactamase Acylation Mechanism Using Neutron and X-ray Crystallography

spinqualitylabelsall models 5a92, resolution 1.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5a92 is a 1 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CEF, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BLC97_ECOLX Publication Abstract from PubMed The catalytic mechanism of class A beta-lactamases is often debated due in part to the large number of amino acids that interact with bound beta-lactam substrates. The role and function of the conserved residue Lys 73 in the catalytic mechanism of class A type beta-lactamase enzymes is still not well understood after decades of scientific research. To better elucidate the functions of this vital residue, we used both neutron and high-resolution X-ray diffraction to examine both the structures of the ligand free protein and the acyl-enzyme complex of perdeuterated E166A Toho-1 beta-lactamase with the antibiotic cefotaxime. The E166A mutant lacks a critical glutamate residue that has a key role in the deacylation step of the catalytic mechanism, allowing the acyl-enzyme adduct to be captured for study. In our ligand free structures, Lys 73 is present in a single conformation, however in all of our acyl-enzyme structures, Lys 73 is present in two different conformations, in which one conformer is closer to Ser 70 while the other conformer is positioned closer to Ser 130, which supports the existence of a possible pathway by which proton transfer from Lys 73 to Ser 130 can occur. This and further clarifications of the role of Lys 73 in the acylation mechanism may facilitate the design of inhibitors that capitalize on the enzyme's native machinery. Exploring the Mechanism of beta-Lactam Ring Protonation in the Class A beta-lactamase Acylation Mechanism Using Neutron and X-ray Crystallography.,Vandavasi VG, Weiss KL, Cooper JB, Erskine PT, Tomanicek SJ, Ostermann A, Schrader TE, Ginell SL, Coates L J Med Chem. 2015 Dec 2. PMID:26630115 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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