Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 차선신 | - |
dc.date.accessioned | 2024-08-30T16:31:16Z | - |
dc.date.available | 2024-08-30T16:31:16Z | - |
dc.date.issued | 2024 | - |
dc.identifier.issn | 9248-8579 | - |
dc.identifier.other | OAK-35558 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/269582 | - |
dc.description.abstract | Objectives: Stenotrophomonas spp. intrinsically resistant to many β-lactam antibiotics are found throughout the environment. CESS-1 identified in Stenotrophomonas sp. KCTC 12332 is an uncharacterized class A β-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 kcat values for cefaclor, cephalexin, and ampicillin were 1249.6 s-1, 204.3 s-1, and 69.8 s-1, respectively, with the accompanying KM values of 287.6 μM, 236.7 μM, and 28.8 μM, respectively. Conclusions: CESS-1 was able to discriminate between cefaclor and cephalexin with a single structural difference at C3 position: –Cl (cefaclor) and –CH3 (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 β5-β6 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 β-lactam antibiotics. © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy | - |
dc.description.sponsorship | Elsevier B.V. | - |
dc.language | English | - |
dc.subject | Acyl-enzyme complexes | - |
dc.subject | Crystal structure | - |
dc.subject | Extended substrate spectrum class A β-lactamase | - |
dc.subject | Steady-state enzyme kinetics | - |
dc.subject | Stenotrophomonas sp. | - |
dc.title | Characterization of the extended substrate spectrum of the class A β-lactamase CESS-1 from Stenotrophomonas sp. and structure-based investigation into its substrate preference | - |
dc.type | Article | - |
dc.relation.issue | 6 | - |
dc.relation.volume | 63 | - |
dc.relation.index | SCIE | - |
dc.relation.index | SCOPUS | - |
dc.relation.journaltitle | International Journal of Antimicrobial Agents | - |
dc.identifier.doi | 10.1016/j.ijantimicag.2024.107171 | - |
dc.identifier.wosid | WOS:001237128700001 | - |
dc.identifier.scopusid | 2-s2.0-85192433234 | - |
dc.author.google | Jeong | - |
dc.author.google | Bo-Gyeong | - |
dc.author.google | Kim | - |
dc.author.google | Myeong-Yeon | - |
dc.author.google | Chang-Sook | - |
dc.author.google | Do | - |
dc.author.google | Hackwon | - |
dc.author.google | Hwang | - |
dc.author.google | Jisub | - |
dc.author.google | Lee | - |
dc.author.google | Jun Hyuck | - |
dc.author.google | Cha | - |
dc.author.google | Sun-Shin | - |
dc.contributor.scopusid | 차선신(7201864593) | - |
dc.date.modifydate | 20240830124230 | - |