8isr | pdb_00008isr

Crystal structure of extended-spectrum class A beta-lactamase, CESS-1 E166Q acylated by cefaclor

spinqualitylabelsall models 8isr, resolution 2.09Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8isr is a 2 chain structure with sequence from Stenotrophomonas sp. KCTC 12332. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.09Å Ligands: EDO, Q6R Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A126NGE0_9GAMM Publication Abstract from PubMed OBJECTIVES: Stenotrophomonas spp. intrinsically resistant to many beta-lactam antibiotics are found throughout the environment. CESS-1 identified in Stenotrophomonas sp. KCTC 12332 is an uncharacterized class A beta-lactamase. The goal of this study was to reveal biochemical and structural characteristics of CESS-1. METHODS: The hydrolytic activities of CESS-1 towards penicillins (penicillin G and ampicillin), cephalosporins (cephalexin, cefaclor, and cefotaxime), and carbapenems (imipenem and meropenem) was spectrophotometrically monitored. Structural information on E166Q mutants of CESS-1 acylated by cefaclor, cephalexin, or ampicillin were determined by X-ray crystallography. RESULTS: CESS-1 displayed hydrolytic activities toward penicillins and cephalosporins, with negligible activity toward carbapenems. Although cefaclor, cephalexin, and ampicillin have similar structures with identical R1 side chains, the catalytic parameters of CESS-1 toward them were distinct. The k(cat) values for cefaclor, cephalexin, and ampicillin were 1249.6 s(-1), 204.3 s(-1), and 69.8 s(-1), respectively, with the accompanying K(M) values of 287.6 muM, 236.7 muM, and 28.8 muM, respectively. CONCLUSIONS: CESS-1 was able to discriminate between cefaclor and cephalexin with a single structural difference at C3 position: -Cl (cefaclor) and -CH(3) (cephalexin). Structural comparisons among three E166Q mutants of CESS-1 acylated by cefaclor, cephalexin, or ampicillin, revealed that cooperative positional changes in the R1 side chain of substrates and their interaction with the beta5-beta6 loop affect the distance between Asn170 and the deacylating water at the acyl-enzyme intermediate state. This is directly associated with the differential hydrolytic activities of CESS-1 toward the three structurally similar beta-lactam antibiotics. Characterization of the extended substrate spectrum of the class A beta-lactamase CESS-1 from Stenotrophomonas sp. and structure-based investigation into its substrate preference.,Jeong BG, Kim MY, Jeong CS, Do H, Hwang J, Lee JH, Cha SS Int J Antimicrob Agents. 2024 Apr 7;63(6):107171. doi: , 10.1016/j.ijantimicag.2024.107171. PMID:38588869 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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