{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:12:30Z","timestamp":1791295950759,"version":"4.1.0"},"reference-count":52,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"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":[[2015,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Infections by fungal pathogens such as\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            and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Aspergillus fumigatus<\/jats:named-content>\n            and their resistance to triazole drugs are major concerns. Fungal lanosterol 14\u03b1-demethylase belongs to the CYP51 class in the cytochrome P450 superfamily of enzymes. This monospanning bitopic membrane protein is involved in ergosterol biosynthesis and is the primary target of azole antifungal drugs, including fluconazole. The lack of high-resolution structural information for this drug target from fungal pathogens has been a limiting factor for the design of modified triazole drugs that will overcome resistance. Here we report the X-ray structure of full-length\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Saccharomyces cerevisiae<\/jats:named-content>\n            lanosterol 14\u03b1-demethylase in complex with fluconazole at a resolution of 2.05 \u00c5. This structure shows the key interactions involved in fluconazole binding and provides insight into resistance mechanisms by revealing a water-mediated hydrogen bonding network between the drug and tyrosine 140, a residue frequently found mutated to histidine or phenylalanine in resistant clinical isolates.\n          <\/jats:p>","DOI":"10.1128\/aac.00925-15","type":"journal-article","created":{"date-parts":[[2015,6,10]],"date-time":"2015-06-10T19:10:15Z","timestamp":1433963415000},"page":"4982-4989","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":210,"title":["Structural Insights into Binding of the Antifungal Drug Fluconazole to Saccharomyces cerevisiae Lanosterol 14\u03b1-Demethylase"],"prefix":"10.1128","volume":"59","author":[{"given":"Alia A.","family":"Sagatova","sequence":"first","affiliation":[{"name":"Sir John Walsh Research Institute, University of Otago, Dunedin, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail V.","family":"Keniya","sequence":"additional","affiliation":[{"name":"Sir John Walsh Research Institute, University of Otago, Dunedin, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajni K.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Sir John Walsh Research Institute, University of Otago, Dunedin, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"Monk","sequence":"additional","affiliation":[{"name":"Sir John Walsh Research Institute, University of Otago, Dunedin, New Zealand"},{"name":"Department of Oral Sciences, Faculty of Dentistry, University of Otago, Dunedin, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel D. 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Amino acid variations of cytochrome P-450 lanosterol 14 alpha-demethylase (CYP51A1) from fluconazoleresistant clinical isolates of Candida albicans. Rev Iberoam Micol 16:198\u2013203.","journal-title":"Rev Iberoam Micol"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1080\/mmy.39.3.299.302"},{"key":"e_1_3_3_53_2","unstructured":"Monk BC Cannon RD Nakamura K Niimi M Niimi K Holmes AR Lamping E Harding DRK Goffeau A Decottignies A. May 2014. Yeast membrane protein expression system and its application in drug screening. 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