Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 이진원 | - |
dc.date.accessioned | 2019-11-22T01:34:56Z | - |
dc.date.available | 2019-11-22T01:34:56Z | - |
dc.date.issued | 2017-03 | - |
dc.identifier.citation | JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, v. 72, no. 3, page. 735-743 | en_US |
dc.identifier.issn | 0305-7453 | - |
dc.identifier.issn | 1460-2091 | - |
dc.identifier.uri | https://academic.oup.com/jac/article/72/3/735/2724578 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/113426 | - |
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. | en_US |
dc.description.sponsorship | This study was supported by National Research Foundation of Korea grants (NRF-2015R1A2A2A01004168 and NRF-2015M1A5A1037480), the KIOST in-house programs (PE99413 and PE99302) and a grant from the Marine Biotechnology Program (PJT200620) funded by the Ministry of Oceans and Fisheries, Korea. Mass spectrometry experiments were supported by a grant from the KRIBB Research Initiative Program. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | OXFORD UNIV PRESS | en_US |
dc.subject | ENTEROBACTER-CLOACAE P99 | en_US |
dc.subject | EXTENDED-SPECTRUM CEPHALOSPORINASES | en_US |
dc.subject | TRANSITION-STATE ANALOG | en_US |
dc.subject | CLASS-A | en_US |
dc.subject | PHOSPHONATE | en_US |
dc.subject | ANTIBIOTICS | en_US |
dc.subject | AVIBACTAM | en_US |
dc.subject | EPIDEMIOLOGY | en_US |
dc.subject | INACTIVATION | en_US |
dc.subject | DERIVATIVES | en_US |
dc.title | Structural and mechanistic insights into the inhibition of class C beta-lactamases through the adenylylation of the nucleophilic serine | en_US |
dc.type | Article | en_US |
dc.relation.no | 3 | - |
dc.relation.volume | 72 | - |
dc.identifier.doi | 10.1093/jac/dkw491 | - |
dc.relation.page | 735-743 | - |
dc.relation.journal | JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY | - |
dc.contributor.googleauthor | Kim, Min-Kyu | - |
dc.contributor.googleauthor | An, Young Jun | - |
dc.contributor.googleauthor | Na, Jung-Hyun | - |
dc.contributor.googleauthor | Seol, Jae-Hee | - |
dc.contributor.googleauthor | Ryu, Ju Yeon | - |
dc.contributor.googleauthor | Lee, Jin-Won | - |
dc.contributor.googleauthor | Kang, Lin-Woo | - |
dc.contributor.googleauthor | Chung, Kyung Min | - |
dc.contributor.googleauthor | Lee, Jung-Hyun | - |
dc.contributor.googleauthor | Moon, Jeong Hee | - |
dc.relation.code | 2017000647 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF NATURAL SCIENCES[S] | - |
dc.sector.department | DEPARTMENT OF LIFE SCIENCE | - |
dc.identifier.pid | jwl | - |
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