The 3-hydroxy group of lanosterol is essential for orienting the substrate site of cytochrome P-450(14DM) (lanosterol 14 alpha- demethylase).
Interaction of lanosterol, 3-epilanosterol, 3-oxolanosta-8,24-diene, 3-methylenelanost-8-ene and lanosterol acetate with cytochrome P-450(14DM) were studied. The cytochrome mediated the 14alpha-demethylation of 3-epilanosterol with nearly the same activity as lanosterol but could not mediate the 14alpha-demethylation of the 3-methylene derivative and the 3-acetate. The cytochrome catalyzed the 14alpha-demethylation of the 3-oxo derivative with low rate. Based on these and some additional observations the hydrogen bond formation between the 3-hydroxy group of lanosterol and the specific amino acid residue in the substrate site is assumed to be essential for orienting the substrate in the substrate site of the cytochrome.
Aoyama
Y
Y
Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
Yoshida
Y
Y
Sonoda
Y
Y
Sato
Y
Y
D055598:Chemical Phenomena; D002621:Chemistry; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006860:Hydrogen Bonding; D007810:Lanosterol / Q000031:analogs & derivatives / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D058886:Sterol 14-Demethylase
D007810:Lanosterol; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase