4jpm | pdb_00004jpm

Structure of SHV-1 beta-lactamase in complex with the 7-alkylidenecephalosporin DCM-1-10 at 1.14 Ang resolution

spinqualitylabelsall models 4jpm, resolution 1.14Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4jpm is a 1 chain structure with sequence from "bacillus_pneumoniae"_(schroeter_1886)_flugge_1886 "bacillus pneumoniae" (schroeter 1886) flugge 1886. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 1OG, EPE, MA4 Related: 4fh4 Gene: bla, shv1 ("Bacillus pneumoniae" (Schroeter 1886) Flugge 1886) Activity: Beta-lactamase, with EC number 3.5.2.6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The inhibition of the class A SHV-1 beta-lactamase by 7-(tert-butoxycarbonyl)methylidenecephalosporin sulfone was examined kinetically, spectroscopically, and crystallographically. An 1.14A X-ray crystal structure shows that the stable acyl-enzyme, which incorporates an eight-membered ring, is a covalent derivative of Ser70 linked to the 7-carboxy group of 2-H-5,8-dihydro-1,1-dioxo-1,5-thiazocine-4,7-dicarboxylic acid. A cephalosporin-derived enzyme complex of this type is unprecedented and the rearrangement leading to its formation may offer new possibilities for inhibitor design. The observed acyl-enzyme derives its stability from the resonance stabilization conveyed by the -aminoacrylate (i.e. vinylogous urethane) functionality as there is relatively little interaction of the eight-membered ring with active site residues. Two mechanistic schemes are proposed, differing in whether, subsequent to acylation of the active site serine and opening of the beta-lactam, the resultant dihydrothiazine fragments on its own, or is assisted by an adjacent nucleophilic atom, in the form of the carbonyl oxygen of the C7 tert-butyloxycarbonyl group. This compound was also found to be a submicromolar inhibitor of the class C ADC-7 and PDC-3 beta-lactamases. beta-Lactamase Inhibition by 7-Alkylidenecephalosporin Sulfones: Allylic Transposition and Formation of an Unprecedented Stabilized Acyl-Enzyme.,Rodkey EA, McLeod DC, Bethel CR, Smith KM, Xu Y, Chai W, Che T, Carey PR, Bonomo RA, van den Akker F, Buynak JD J Am Chem Soc. 2013 Nov 12. PMID:24219313 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase

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