DC Field | Value | Language |
---|---|---|
dc.contributor.author | Chung, Scisung | - |
dc.contributor.author | Kim, Sulhee | - |
dc.contributor.author | Ryu, Sung Ho | - |
dc.contributor.author | Hwang, Kwang Yeon | - |
dc.contributor.author | Cho, Yunje | - |
dc.date.accessioned | 2021-12-03T09:43:39Z | - |
dc.date.available | 2021-12-03T09:43:39Z | - |
dc.date.created | 2020-05-21 | - |
dc.date.issued | 2020-04 | - |
dc.identifier.issn | 1016-8478 | - |
dc.identifier.uri | https://oasis.postech.ac.kr/handle/2014.oak/107903 | - |
dc.description.abstract | Pathogenic aminoacyl-tRNA synthetases (ARSs) are attractive targets for anti-infective agents because their catalytic active sites are different from those of human ARSs. Mupirocin is a topical antibiotic that specifically inhibits bacterial isoleucyl-tRNA synthetase (IleRS), resulting in a block to protein synthesis. Previous studies on Thermus thermophilus IleRS indicated that mupirocin-resistance of eukaryotic IleRS is primarily due to differences in two amino acids, His581 and Leu583, in the active site. However, without a eukaryotic IleRS structure, the structural basis for mupirocin-resistance of eukaryotic IleRS remains elusive. Herein, we determined the crystal structure of Candida albicans IleRS complexed with Ile-AMP at 2.9 A resolution. The largest difference between eukaryotic and prokaryotic IleRS enzymes is closure of the active site pocket by Phe55 in the HIGH loop; Arg410 in the CP core loop; and the second Lys in the KMSKR loop. The Ile-AMP product is lodged in a closed active site, which may restrict its release and thereby enhance catalytic efficiency. The compact active site also prevents the optimal positioning of the 9-hydroxynonanoic acid of mupirocin and plays a critical role in resistance of eukaryotic IleRS to anti-infective agents. | - |
dc.language | English | - |
dc.publisher | KOREAN SOC MOLECULAR & CELLULAR BIOLOGY | - |
dc.relation.isPartOf | MOLECULES AND CELLS | - |
dc.title | Structural Basis for the Antibiotic Resistance Eukaryotic Isoleucyl-tRNA Synthetase | - |
dc.type | Article | - |
dc.identifier.doi | 10.14348/molcells.2020.2287 | - |
dc.type.rims | ART | - |
dc.identifier.bibliographicCitation | MOLECULES AND CELLS, v.43, no.4, pp.350 - 359 | - |
dc.identifier.wosid | 000528946600005 | - |
dc.citation.endPage | 359 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 350 | - |
dc.citation.title | MOLECULES AND CELLS | - |
dc.citation.volume | 43 | - |
dc.contributor.affiliatedAuthor | Chung, Scisung | - |
dc.contributor.affiliatedAuthor | Ryu, Sung Ho | - |
dc.contributor.affiliatedAuthor | Cho, Yunje | - |
dc.identifier.scopusid | 2-s2.0-85084026503 | - |
dc.description.journalClass | 1 | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | ESCHERICHIA-COLI | - |
dc.subject.keywordPlus | PSEUDOMONIC ACID | - |
dc.subject.keywordPlus | RECOGNITION | - |
dc.subject.keywordPlus | ADENYLATE | - |
dc.subject.keywordPlus | MUPIROCIN | - |
dc.subject.keywordPlus | COMPLEX | - |
dc.subject.keywordPlus | MODEL | - |
dc.subject.keywordAuthor | active site closure | - |
dc.subject.keywordAuthor | aminoacyl-tRNA synthetases | - |
dc.subject.keywordAuthor | anti-infective agents | - |
dc.subject.keywordAuthor | crystal structure | - |
dc.subject.keywordAuthor | mupirocin | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kci | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Cell Biology | - |
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