5cgx | pdb_00005cgx

CRYSTAL STRUCTURE OF Fox-4 cephamycinase mutant Y150F complexed with cefoxitin

spinqualitylabelsall models 5cgx, resolution 1.21Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5cgx 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. Method: X-ray diffraction, Resolution 1.21Å Ligands: 1S7, NA, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9L387_ECOLX Publication Abstract from PubMed Class C beta-lactamases poorly hydrolyze cephamycins (e.g., cefoxitin, cefotetan, and moxalactam). In the past 2 decades, a new family of plasmid-based AmpC beta-lactamases conferring resistance to cefoxitin, the FOX family, has grown to include nine unique members descended from the Aeromonas caviae chromosomal AmpC. To understand the basis for the unique cephamycinase activity in the FOX family, we determined the first X-ray crystal structures of FOX-4, apo enzyme and the acyl-enzyme with its namesake compound, cefoxitin, using the Y150F deacylation-deficient variant. Notably, recombinant expression of N-terminally tagged FOX-4 also yielded an inactive adenylylated enzyme form not previously observed in beta-lactamases. The posttranslational modification (PTM), which occurs on the active site Ser64, would not seem to provide a selective advantage, yet might present an opportunity for the design of novel antibacterial drugs. Substantial ligand-induced changes in the enzyme are seen in the acyl-enzyme complex, particularly the R2 loop and helix H10 (P289 to N297), with movement of F293 by 10.3 A. Taken together, this study provides the first picture of this highly proficient class C cephamycinase, uncovers a novel PTM, and suggests a possible cephamycin resistance mechanism involving repositioning of the substrate due to the presence of S153P, N289P, and N346I substitutions in the ligand binding pocket. Analysis of the Structure and Function of FOX-4 Cephamycinase.,Lefurgy ST, Malashkevich VN, Aguilan JT, Nieves E, Mundorff EC, Biju B, Noel MA, Toro R, Baiwir D, Papp-Wallace KM, Almo SC, Frere JM, Bou G, Bonomo RA Antimicrob Agents Chemother. 2015 Nov 2;60(2):717-28. doi: 10.1128/AAC.01887-15. PMID:26525784 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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