{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:59:16Z","timestamp":1790949556637,"version":"4.1.0"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,2,17]]},"abstract":"<jats:p>\n                    Inhibitors of the last steps of cholesterol biosynthesis such as AY9944 and BM15766 severely impair brain development. Their molecular target is the \u03947-sterol reductase (EC\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"ec\" xlink:href=\"1.3.1.21\">1.3.1.21<\/jats:ext-link>\n                    ), suspected to be defective in the Smith\u2013Lemli\u2013Opitz syndrome, a frequent inborn disorder of sterol metabolism. Molecular cloning of the cDNA revealed that the human enzyme is a membrane-bound protein with a predicted molecular mass of 55 kDa and six to nine putative transmembrane segments. The protein is structurally related to plant and yeast sterol reductases. In adults the ubiquitously transcribed mRNA is most abundant in adrenal gland, liver, testis, and brain. The \u03947-sterol reductase is the ultimate enzyme of cholesterol biosynthesis in vertebrates and is absent from yeast. Microsomes from\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    strains heterologously expressing the human cDNA remove the C\n                    <jats:sub>7\u20138<\/jats:sub>\n                    double bond in 7-dehydrocholesterol. The conversion to cholesterol depends on NADPH and is potently inhibited by AY9944 (IC\n                    <jats:sub>50<\/jats:sub>\n                    0.013 \u03bcM), BM15766 (IC\n                    <jats:sub>50<\/jats:sub>\n                    1.2 \u03bcM), and triparanol (IC\n                    <jats:sub>50<\/jats:sub>\n                    14 \u03bcM). Our work paves the way to clarify whether a defect in the \u03947-sterol reductase gene underlies the Smith\u2013Lemli\u2013Opitz syndrome.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.4.1899","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:50Z","timestamp":1027679750000},"page":"1899-1902","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":194,"title":["Molecular cloning and expression of the human \u03947-sterol reductase"],"prefix":"10.1073","volume":"95","author":[{"given":"Fabian F.","family":"Moebius","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Biochemische Pharmakologie, Universit\u00e4t Innsbruck, Peter Mayr Str. 1, A-6020 Innsbruck, Austria; and Department of Biochemistry and Bioproducts Research Center, Yonsei University, Seoul 120-749, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara 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