Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 차선신 | * |
dc.date.accessioned | 2018-12-07T16:30:49Z | - |
dc.date.available | 2018-12-07T16:30:49Z | - |
dc.date.issued | 2017 | * |
dc.identifier.issn | 1460-2091 | * |
dc.identifier.other | OAK-20506 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/247438 | - |
dc.description.abstract | Objectives: : Investigation into the adenylylation of the nucleophilic serine in AmpC BER and CMY-10 extended-spectrum class C β-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 5'-(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 be modelled as a two-step mechanism. 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 mechanism of adenylylation of the nucleophilic serine and may serve as a starting point for the design of novel class C β-lactamase inhibitors on the basis of the nucleotide scaffold. | * |
dc.language | English | * |
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.relation.issue | 3 | * |
dc.relation.volume | 72 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 735 | * |
dc.relation.lastpage | 743 | * |
dc.relation.journaltitle | The Journal of antimicrobial chemotherapy | * |
dc.identifier.doi | 10.1093/jac/dkw491 | * |
dc.identifier.wosid | WOS:000398038800012 | * |
dc.identifier.scopusid | 2-s2.0-85018181572 | * |
dc.author.google | Kim M.-K. | * |
dc.author.google | An Y.J. | * |
dc.author.google | Na J.-H. | * |
dc.author.google | Seol J.-H. | * |
dc.author.google | Ryu J.Y. | * |
dc.author.google | Lee J.-W. | * |
dc.author.google | Kang L.-W. | * |
dc.author.google | Chung K.M. | * |
dc.author.google | Lee J.-H. | * |
dc.author.google | Moon J.H. | * |
dc.author.google | Lee J.S. | * |
dc.author.google | Cha S.-S. | * |
dc.contributor.scopusid | 차선신(7201864593) | * |
dc.date.modifydate | 20240429134916 | * |