Molecular cloning of the human gene encoding lanosterol synthase from a liver cDNA library.
Lanosterol synthase [(S)-2,3-epoxysqualene mutase (cyclizing, lanosterol forming), EC 5.4.99.7] catalyzes the cyclization of (S)-2,3-oxidosqualene to lanosterol in the reaction that forms the sterol nucleus. We report herein the cloning and characterization of the human gene (OSC) encoding lanosterol synthase, a predicted 83 kDa protein of 732 amino acids. The deduced amino acid sequence is 36-40% identical to known yeast and plant homologues and 83% identical to Rattus norvegicus lanosterol synthase. The new gene was shown to encode lanosterol synthase. The yeast lanosterol synthase deficient mutant SMY8 was complemented by the human gene, and a cell-free homogenate of SMY8 expressing the human gene was shown to convert 2,3-oxidosqualene to lanosterol.
Baker
C H
CH
Department of Chemistry, Harvard University, Cambridge, MA 02138, USA.
Matsuda
S P
SP
Liu
D R
DR
Corey
E J
EJ
D000595:Amino Acid Sequence; D000818:Animals; D017360:Arabidopsis / Q000201:enzymology; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004926:Escherichia coli; D015723:Gene Library; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D019751:Intramolecular Transferases; D007535:Isomerases / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D051381:Rats; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D007535:Isomerases; D019751:Intramolecular Transferases; C021924:lanosterol synthase