Structural and mechanistic insights into the inhibition of class C β-lactamases through the adenylylation of the nucleophilic serine
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Min-Kyu | - |
dc.contributor.author | An, Young Jun | - |
dc.contributor.author | Na, Jung-Hyun | - |
dc.contributor.author | Seol, Jae-Hee | - |
dc.contributor.author | Ryu, Ju Yeon | - |
dc.contributor.author | Lee, Jin-Won | - |
dc.contributor.author | Kang, Lin-Woo | - |
dc.contributor.author | Chung, Kyung Min | - |
dc.contributor.author | Lee, Jung-Hyun | - |
dc.contributor.author | Moon, Jeong Hee | - |
dc.contributor.author | Lee, Jong Seok | - |
dc.contributor.author | Cha, Sun-Shin | - |
dc.date.accessioned | 2021-08-02T15:31:22Z | - |
dc.date.available | 2021-08-02T15:31:22Z | - |
dc.date.created | 2021-05-11 | - |
dc.date.issued | 2017-03 | - |
dc.identifier.issn | 0305-7453 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/20537 | - |
dc.description.abstract | Objectives: Investigation into the adenylylation of the nucleophilic serine in AmpC BER and CMY-10 extended spectrumclass C beta-lactamases. Methods: The formation and the stability of the adenylate adduct were examined by X-ray crystallography and MS. Inhibition assays for kinetic parameters were performed by monitoring the hydrolytic activity of AmpC BER and CMY-10 using nitrocefin as a reporter substrate. The effect of adenosine 50'-(P-acetyl) monophosphate ( acAMP) on the MIC of ceftazidime was tested with four Gram-negative clinical isolates. Results: The crystal structures and MS analyses confirmed the acAMP-mediated adenylylation of the nucleophilic serine in AmpC BER and CMY-10. acAMP inhibited AmpC BER and CMY-10 through the adenylylation of the nucleophilic serine, which could bemodelled as a two-stepmechanism. The initial non-covalent binding of acAMP to the active site is followed by the covalent attachment of its AMP moiety to the nucleophilic serine. The inhibition efficiencies (k(inact)/K-I) of acAMP against AmpC BER and CMY-10 were determined to be 320 and 140 M(-1)s(-1), respectively. The combination of ceftazidime and acAMP reduced the MIC of ceftazidime against the tested bacteria. Conclusions: Our structural and kinetic studies revealed the detailed mechanismof adenylylation of the nucleophilic serine and may serve as a starting point for the design of novel class C beta-lactamase inhibitors on the basis of the nucleotide scaffold. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | OXFORD UNIV PRESS | - |
dc.title | Structural and mechanistic insights into the inhibition of class C β-lactamases through the adenylylation of the nucleophilic serine | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Jin-Won | - |
dc.identifier.doi | 10.1093/jac/dkw491 | - |
dc.identifier.scopusid | 2-s2.0-85018181572 | - |
dc.identifier.wosid | 000398038800012 | - |
dc.identifier.bibliographicCitation | JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, v.72, no.3, pp.735 - 743 | - |
dc.relation.isPartOf | JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY | - |
dc.citation.title | JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY | - |
dc.citation.volume | 72 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 735 | - |
dc.citation.endPage | 743 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Infectious Diseases | - |
dc.relation.journalResearchArea | Microbiology | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Infectious Diseases | - |
dc.relation.journalWebOfScienceCategory | Microbiology | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | ENTEROBACTER-CLOACAE P99 | - |
dc.subject.keywordPlus | EXTENDED-SPECTRUM CEPHALOSPORINASES | - |
dc.subject.keywordPlus | TRANSITION-STATE ANALOG | - |
dc.subject.keywordPlus | CLASS-A | - |
dc.subject.keywordPlus | PHOSPHONATE | - |
dc.subject.keywordPlus | ANTIBIOTICS | - |
dc.subject.keywordPlus | AVIBACTAM | - |
dc.subject.keywordPlus | EPIDEMIOLOGY | - |
dc.subject.keywordPlus | INACTIVATION | - |
dc.subject.keywordPlus | DERIVATIVES | - |
dc.subject.keywordAuthor | Anti-Bacterial Agents | - |
dc.subject.keywordAuthor | Bacterial Proteins | - |
dc.subject.keywordAuthor | beta-Lactamase Inhibitors | - |
dc.subject.keywordAuthor | beta-Lactamases | - |
dc.subject.keywordAuthor | Ceftazidime | - |
dc.subject.keywordAuthor | Crystallography, X-Ray | - |
dc.subject.keywordAuthor | Kinetics | - |
dc.subject.keywordAuthor | Microbial Sensitivity Tests | - |
dc.subject.keywordAuthor | Serine | - |
dc.identifier.url | https://academic.oup.com/jac/article/72/3/735/2724578 | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
222, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Korea+82-2-2220-1365
COPYRIGHT © 2021 HANYANG UNIVERSITY.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.