Heterologous expression and characterization of the sterol 14 alpha-demethylase CYP51F1 from Candida albicans
DC Field | Value | Language |
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dc.contributor.author | Park, Hyoung-Goo | - |
dc.contributor.author | Lee, Im-Soon | - |
dc.contributor.author | Chun, Young-Jin | - |
dc.contributor.author | Yun, Chul-Ho | - |
dc.contributor.author | Johnston, Jonathan B. | - |
dc.contributor.author | de Montellano, Paul R. Ortiz | - |
dc.contributor.author | Kim, Donghak | - |
dc.date.available | 2019-05-29T13:34:38Z | - |
dc.date.issued | 2011-05 | - |
dc.identifier.issn | 0003-9861 | - |
dc.identifier.issn | 1096-0384 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/21545 | - |
dc.description.abstract | Lanosterol 14 alpha-demethylase (CYP51F1) from Candida albicans is known to be an essential enzyme in fungal sterol biosynthesis. Wild-type CYP51F1 and several of its mutants were heterologously expressed in Escherichia coli, purified, and characterized. It exhibited a typical reduced CO-difference spectrum with a maximum at 446 nm. Reconstitution of CYP51F1 with NADPH-P450 reductase gave a system that successfully converted lanosterol to its demethylated product. Titration of the purified enzyme with lanosterol produced a typical type I spectral change with K-d = 6.7 mu M. The azole antifungal agents econazole, fluconazole, ketoconazole, and itraconazole bound tightly to CYP51F1 with K-d values between 0.06 and 0.42 mu M. The CYP51F1 mutations F105L, D116E, Y132H, and R467K frequently identified in clinical isolates were examined to determine their effect on azole drug binding affinity. The azole K-d values of the purified F105L, D116E, and R467K mutants were little altered. A homology model of C. albicans CYP51F1 suggested that Tyr132 in the BC loop is located close to the heme in the active site, providing a rationale for the modified heme environment caused by the Y132H substitution. Taken together, functional expression and characterization of CYP51F1 provide a starting basis for the design of agents effective against C. albicans infections. (C) 2011 Elsevier Inc. All rights reserved. | - |
dc.format.extent | 7 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | ELSEVIER SCIENCE INC | - |
dc.title | Heterologous expression and characterization of the sterol 14 alpha-demethylase CYP51F1 from Candida albicans | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.abb.2011.02.002 | - |
dc.identifier.bibliographicCitation | ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, v.509, no.1, pp 9 - 15 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000289928800002 | - |
dc.identifier.scopusid | 2-s2.0-79954438596 | - |
dc.citation.endPage | 15 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 9 | - |
dc.citation.title | ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | - |
dc.citation.volume | 509 | - |
dc.type.docType | Article | - |
dc.publisher.location | 미국 | - |
dc.subject.keywordAuthor | P450 | - |
dc.subject.keywordAuthor | CYP51 | - |
dc.subject.keywordAuthor | Lanosterol | - |
dc.subject.keywordAuthor | Azole | - |
dc.subject.keywordAuthor | Candida albicans | - |
dc.subject.keywordPlus | HUMAN CYTOCHROME-P450 1A2 | - |
dc.subject.keywordPlus | ANTIFUNGAL AGENTS | - |
dc.subject.keywordPlus | AZOLE RESISTANCE | - |
dc.subject.keywordPlus | HYDROXYLATION | - |
dc.subject.keywordPlus | SUBSTITUTIONS | - |
dc.subject.keywordPlus | SUPERFAMILY | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | OXIDATION | - |
dc.subject.keywordPlus | SELECTION | - |
dc.subject.keywordPlus | MUTANTS | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Biophysics | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biophysics | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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