Elucidation of Allosteric Inhibition Mechanism of 2-Cys Human Peroxiredoxin by Molecular Modeling
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Minsup | - |
dc.contributor.author | Lee, Keun Woo | - |
dc.contributor.author | Cho, Art E. | - |
dc.date.accessioned | 2021-09-06T12:20:30Z | - |
dc.date.available | 2021-09-06T12:20:30Z | - |
dc.date.created | 2021-06-14 | - |
dc.date.issued | 2012-12 | - |
dc.identifier.issn | 1549-9596 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/106729 | - |
dc.description.abstract | We used molecular dynamics (MD) simulations and protein docking to elucidate the mechanism of allosteric inhibition of the human form of peroxiredoxin (Prx), 2-Cys proliferation associated gene (PAG). Beginning by using the rat form of Prx, 2-Cys heme-binding protein as a template, we used homology modeling to find the structure of human 2-Cys PAG, which is in dimeric form. Molecular dynamics simulations showed that the structure of the reduced form of the 2-Cys PAG dimer fluctuates as the two monomers drift away and approach each other. We then used SiteMap to search for binding sites on the surface of this dimer. A binding site between the two monomers was found, and virtual screening with docking was performed to identify a ligand binding to this site. Subsequent MD simulation revealed that with this ligand in the binding site, the dimer structure of 2-Cys PAG becomes stabilized such that two cysteine residues from two monomers, which are partners of a disulfide bond of the oxidized form, remain separated. This mechanism can be used as an allosteric inhibition of Prx as a hydrogen peroxide reducer, the role of which has been studied as an anticancer drug target. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.subject | CRYSTAL-STRUCTURE | - |
dc.subject | MAMMALIAN PEROXIREDOXIN | - |
dc.subject | ANGSTROM RESOLUTION | - |
dc.subject | BREAST-CANCER | - |
dc.subject | LUNG-CANCER | - |
dc.subject | PROTEIN | - |
dc.subject | THIOREDOXIN | - |
dc.subject | ANTIOXIDANT | - |
dc.subject | CELLS | - |
dc.subject | OXIDOREDUCTASES | - |
dc.title | Elucidation of Allosteric Inhibition Mechanism of 2-Cys Human Peroxiredoxin by Molecular Modeling | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Cho, Art E. | - |
dc.identifier.doi | 10.1021/ci3004495 | - |
dc.identifier.scopusid | 2-s2.0-84871535862 | - |
dc.identifier.wosid | 000312563800017 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CHEMICAL INFORMATION AND MODELING, v.52, no.12, pp.3278 - 3283 | - |
dc.relation.isPartOf | JOURNAL OF CHEMICAL INFORMATION AND MODELING | - |
dc.citation.title | JOURNAL OF CHEMICAL INFORMATION AND MODELING | - |
dc.citation.volume | 52 | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 3278 | - |
dc.citation.endPage | 3283 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalResearchArea | Computer Science | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.relation.journalWebOfScienceCategory | Computer Science, Information Systems | - |
dc.relation.journalWebOfScienceCategory | Computer Science, Interdisciplinary Applications | - |
dc.subject.keywordPlus | CRYSTAL-STRUCTURE | - |
dc.subject.keywordPlus | MAMMALIAN PEROXIREDOXIN | - |
dc.subject.keywordPlus | ANGSTROM RESOLUTION | - |
dc.subject.keywordPlus | BREAST-CANCER | - |
dc.subject.keywordPlus | LUNG-CANCER | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | THIOREDOXIN | - |
dc.subject.keywordPlus | ANTIOXIDANT | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | OXIDOREDUCTASES | - |
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.