Non-catalytic-Region Mutations Conferring Transition of Class A beta-Lactamases Into ESBLs
DC Field | Value | Language |
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dc.contributor.author | Cao, Thinh-Phat | - |
dc.contributor.author | Yi, Hyojeong | - |
dc.contributor.author | Dhanasingh, Immanuel | - |
dc.contributor.author | Ghosh, Suparna | - |
dc.contributor.author | Choi, Jin Myung | - |
dc.contributor.author | Lee, Kun Ho | - |
dc.contributor.author | Ryu, Seol | - |
dc.contributor.author | Kim, Heenam Stanley | - |
dc.contributor.author | Lee, Sung Haeng | - |
dc.date.accessioned | 2021-08-30T07:53:50Z | - |
dc.date.available | 2021-08-30T07:53:50Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2020-11-27 | - |
dc.identifier.issn | 2296-889X | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/51444 | - |
dc.description.abstract | Despite class A ESBLs carrying substitutions outside catalytic regions, such as Cys69Tyr or Asn136Asp, have emerged as new clinical threats, the molecular mechanisms underlying their acquired antibiotics-hydrolytic activity remains unclear. We discovered that this non-catalytic-region (NCR) mutations induce significant dislocation of beta 3-beta 4 strands, conformational changes in critical residues associated with ligand binding to the lid domain, dynamic fluctuation of omega-loop and beta 3-beta 4 elements. Such structural changes increase catalytic regions' flexibility, enlarge active site, and thereby accommodate third-generation cephalosporin antibiotics, ceftazidime (CAZ). Notably, the electrostatic property around the oxyanion hole of Cys69Tyr ESBL is significantly changed, resulting in possible additional stabilization of the acyl-enzyme intermediate. Interestingly, the NCR mutations are as effective for antibiotic resistance by altering the structure and dynamics in regions mediating substrate recognition and binding as single amino-acid substitutions in the catalytic region of the canonical ESBLs. We believe that our findings are crucial in developing successful therapeutic strategies against diverse class A ESBLs, including the new NCR-ESBLs. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | FRONTIERS MEDIA SA | - |
dc.subject | SITE-DIRECTED MUTAGENESIS | - |
dc.subject | ANTIBIOTIC-RESISTANCE | - |
dc.subject | MOLECULAR-DYNAMICS | - |
dc.subject | OMEGA-LOOP | - |
dc.subject | SUBSTRATE | - |
dc.subject | MUTANT | - |
dc.subject | SUBSTITUTION | - |
dc.subject | CEFTAZIDIME | - |
dc.subject | REFINEMENT | - |
dc.subject | EVOLUTION | - |
dc.title | Non-catalytic-Region Mutations Conferring Transition of Class A beta-Lactamases Into ESBLs | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Heenam Stanley | - |
dc.identifier.doi | 10.3389/fmolb.2020.598998 | - |
dc.identifier.scopusid | 2-s2.0-85097659923 | - |
dc.identifier.wosid | 000598867600001 | - |
dc.identifier.bibliographicCitation | FRONTIERS IN MOLECULAR BIOSCIENCES, v.7 | - |
dc.relation.isPartOf | FRONTIERS IN MOLECULAR BIOSCIENCES | - |
dc.citation.title | FRONTIERS IN MOLECULAR BIOSCIENCES | - |
dc.citation.volume | 7 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.subject.keywordPlus | SITE-DIRECTED MUTAGENESIS | - |
dc.subject.keywordPlus | ANTIBIOTIC-RESISTANCE | - |
dc.subject.keywordPlus | MOLECULAR-DYNAMICS | - |
dc.subject.keywordPlus | OMEGA-LOOP | - |
dc.subject.keywordPlus | SUBSTRATE | - |
dc.subject.keywordPlus | MUTANT | - |
dc.subject.keywordPlus | SUBSTITUTION | - |
dc.subject.keywordPlus | CEFTAZIDIME | - |
dc.subject.keywordPlus | REFINEMENT | - |
dc.subject.keywordPlus | EVOLUTION | - |
dc.subject.keywordAuthor | extended-spectrum & | - |
dc.subject.keywordAuthor | #946 | - |
dc.subject.keywordAuthor | -lactamase | - |
dc.subject.keywordAuthor | non-catalytic-region ESBL | - |
dc.subject.keywordAuthor | ceftazidime | - |
dc.subject.keywordAuthor | antibiotic resistance | - |
dc.subject.keywordAuthor | X-ray crystallography | - |
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