Twelve Positions in a beta-Lactamase That Can Expand Its Substrate Spectrum with a Single Amino Acid Substitution
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Yi, Hyojeong | - |
dc.contributor.author | Cho, Kwang-Hwi | - |
dc.contributor.author | Cho, Yun Sung | - |
dc.contributor.author | Kim, Karan | - |
dc.contributor.author | Nierman, William C. | - |
dc.contributor.author | Kim, Heenam Stanley | - |
dc.date.accessioned | 2021-09-06T19:44:26Z | - |
dc.date.available | 2021-09-06T19:44:26Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2012-05-22 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/108403 | - |
dc.description.abstract | The continuous evolution of beta-lactamases resulting in bacterial resistance to beta-lactam antibiotics is a major concern in public health, and yet the underlying molecular basis or the pattern of such evolution is largely unknown. We investigated the mechanics of the substrate fspectrum expansion of the class A beta-lactamase using PenA of Burkholderia thailandensis as a model. By analyzing 516 mutated enzymes that acquired the ceftazidime-hydrolyzing activity, we found twelve positions with single amino acid substitutions (altogether twenty-nine different substitutions), co-localized at the active-site pocket area. The ceftazidime MIC (minimum inhibitory concentration) levels and the relative frequency in the occurrence of substitutions did not correlate well with each other, and the latter appeared be largely influenced by the intrinsic mutational biases present in bacteria. Simulation studies suggested that all substitutions caused a congruent effect, expanding the space in a conserved structure called the omega loop, which in turn increased flexibility at the active site. A second phase of selection, in which the mutants were placed under increased antibiotic pressure, did not result in a second mutation in the coding region, but a mutation that increased gene expression arose in the promoter. This result suggests that the twelve amino acid positions and their specific substitutions in PenA may represent a comprehensive repertoire of the enzyme's adaptability to a new substrate. These mapped substitutions represent a comprehensive set of general mechanical paths to substrate spectrum expansion in class A beta-lactamases that all share a functional evolutionary mechanism using common conserved residues. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | PUBLIC LIBRARY SCIENCE | - |
dc.subject | BURKHOLDERIA-PSEUDOMALLEI | - |
dc.subject | ANTIMICROBIAL SUSCEPTIBILITY | - |
dc.subject | ANTIBIOTIC-RESISTANCE | - |
dc.subject | CEFTAZIDIME | - |
dc.subject | EVOLUTION | - |
dc.subject | MUTATIONS | - |
dc.title | Twelve Positions in a beta-Lactamase That Can Expand Its Substrate Spectrum with a Single Amino Acid Substitution | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Heenam Stanley | - |
dc.identifier.doi | 10.1371/journal.pone.0037585 | - |
dc.identifier.scopusid | 2-s2.0-84861308615 | - |
dc.identifier.wosid | 000305345300055 | - |
dc.identifier.bibliographicCitation | PLOS ONE, v.7, no.5 | - |
dc.relation.isPartOf | PLOS ONE | - |
dc.citation.title | PLOS ONE | - |
dc.citation.volume | 7 | - |
dc.citation.number | 5 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | BURKHOLDERIA-PSEUDOMALLEI | - |
dc.subject.keywordPlus | ANTIMICROBIAL SUSCEPTIBILITY | - |
dc.subject.keywordPlus | ANTIBIOTIC-RESISTANCE | - |
dc.subject.keywordPlus | CEFTAZIDIME | - |
dc.subject.keywordPlus | EVOLUTION | - |
dc.subject.keywordPlus | MUTATIONS | - |
dc.subject.keywordAuthor | GRAM-NEGATIVE BACTERIA | - |
dc.subject.keywordAuthor | BURKHOLDERIA-PSEUDOMALLEI | - |
dc.subject.keywordAuthor | ANTIMICROBIAL SUSCEPTIBILITY | - |
dc.subject.keywordAuthor | PSEUDOMONAS-AERUGINOSA | - |
dc.subject.keywordAuthor | ANTIBIOTIC-RESISTANCE | - |
dc.subject.keywordAuthor | ESCHERICHIA-COLI | - |
dc.subject.keywordAuthor | CEFTAZIDIME | - |
dc.subject.keywordAuthor | EVOLUTION | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(02841) 서울특별시 성북구 안암로 14502-3290-1114
COPYRIGHT © 2021 Korea University. All Rights Reserved.
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.