{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:40:14Z","timestamp":1773812414238,"version":"3.50.1"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2012,4,1]],"date-time":"2012-04-01T00:00:00Z","timestamp":1333238400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The effects of S279F and S279Y point mutations in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida albicans<\/jats:named-content>\n            CYP51 (CaCYP51) on protein activity and on substrate (lanosterol) and azole antifungal binding were investigated. Both S279F and S279Y mutants bound lanosterol with 2-fold increased affinities (\n            <jats:italic>\n              K\n              <jats:sub>s<\/jats:sub>\n            <\/jats:italic>\n            , 7.1 and 8.0 \u03bcM, respectively) compared to the wild-type CaCYP51 protein (\n            <jats:italic>\n              K\n              <jats:sub>s<\/jats:sub>\n            <\/jats:italic>\n            , 13.5 \u03bcM). The S279F and S279Y mutants and the wild-type CaCYP51 protein bound fluconazole, voriconazole, and itraconazole tightly, producing typical type II binding spectra. However, the S279F and S279Y mutants had 4- to 5-fold lower affinities for fluconazole, 3.5-fold lower affinities for voriconazole, and 3.5- to 4-fold lower affinities for itraconazole than the wild-type CaCYP51 protein. The S279F and S279Y mutants gave 2.3- and 2.8-fold higher 50% inhibitory concentrations (IC\n            <jats:sub>50<\/jats:sub>\n            s) for fluconazole in a CYP51 reconstitution assay than the wild-type protein did. The increased fluconazole resistance conferred by the S279F and S279Y point mutations appeared to be mediated through a combination of a higher affinity for substrate and a lower affinity for fluconazole. In addition, lanosterol displaced fluconazole from the S279F and S279Y mutants but not from the wild-type protein. Molecular modeling of the wild-type protein indicated that the oxygen atom of S507 interacts with the second triazole ring of fluconazole, assisting in orientating fluconazole so that a more favorable binding conformation to heme is achieved. In contrast, in the two S279 mutant proteins, this S507-fluconazole interaction is absent, providing an explanation for the higher\n            <jats:italic>K<\/jats:italic>\n            <jats:sub>d<\/jats:sub>\n            values observed.\n          <\/jats:p>","DOI":"10.1128\/aac.05389-11","type":"journal-article","created":{"date-parts":[[2012,1,18]],"date-time":"2012-01-18T05:13:08Z","timestamp":1326863588000},"page":"2099-2107","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["S279 Point Mutations in Candida albicans Sterol 14-\u03b1 Demethylase (CYP51) Reduce\n            <i>In Vitro<\/i>\n            Inhibition by Fluconazole"],"prefix":"10.1128","volume":"56","author":[{"given":"Andrew G. 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