3isg

Structure of the class D beta-lactamase OXA-1 in complex with doripenem

spinqualitylabelsall models 3isg, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3isg is a 2 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: DRW, MPD NonStd Res: KCX Gene: bla, oxa1 ("Bacillus coli" Migula 1895) Activity: Beta-lactamase, with EC number 3.5.2.6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [BLO1_ECOLX] This is an oxacillin-hydrolyzing beta-lactamase. 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 The clinical efficacy of carbapenem antibiotics depends on their resistance to the hydrolytic action of beta-lactamase enzymes. The structure of the class D beta-lactamase OXA-1 as an acyl complex with the carbapenem doripenem was determined to 1.4 A resolution. Unlike most class A and class C carbapenem complexes, the acyl carbonyl oxygen in the OXA-1-doripenem complex is bound in the oxyanion hole. Interestingly, no water molecules were observed in the vicinity of the acyl linkage, providing an explanation for why carbapenems inhibit OXA-1. The side chain amine of K70 remains fully carboxylated in the acyl structure, and the resulting carbamate group forms a hydrogen bond to the alcohol of the 6alpha-hydroxyethyl moiety of doripenem. The carboxylate attached to the beta-lactam ring of doripenem is stabilized by a salt bridge to K212 and a hydrogen bond with T213, in lieu of the interaction with an arginine side chain found in most other beta-lactamase-beta-lactam complexes (e.g., R244 in the class A member TEM-1). This novel set of interactions with the carboxylate results in a major shift of the carbapenem's pyrroline ring compared to the structure of the same ring in meropenem bound to OXA-13. Additionally, bond angles of the pyrroline ring suggest that after acylation, doripenem adopts the Delta(1) tautomer. These findings provide important insights into the role that carbapenems may have in the inactivation process of class D beta-lactamases. The 1.4 A Crystal Structure of the Class D beta-Lactamase OXA-1 Complexed with Doripenem.,Schneider KD, Karpen ME, Bonomo RA, Leonard DA, Powers RA Biochemistry. 2009 Nov 24. PMID:19919101 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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