566-14-3Relevant articles and documents
Sterol C24-methyltransferase: Physio- and stereo-chemical features of the sterol C3 group required for catalytic competence
Howard, Alicia L.,Liu, Jialin,Elmegeed, Gamal A.,Collins, Emily K.,Ganatra, Kalgi S.,Nwogwugwu, Chizaram A.,Nes, W. David
, p. 43 - 50 (2012/08/07)
Sterol C24-methyltransferases (24-SMTs) catalyze the electrophilic alkylation of Δ24-sterols to a variety of sterol side chain constructions, and the C3- moiety is the primary determinant for substrate binding by these enzymes. To determine what specific structural features of the C3-polar group ensure sterol catalysis, a series of structurally related C3-analogs of lanosterol that differed in stereochemistry, bulk and electronic properties were examined against the fungal 24-SMT from Paracoccidioides brasiliensis (Pb) which recognize lanosterol as the natural substrate. Analysis of the magnitude of sterol C24-methylation activity (based on the kinetic constants of Vmax/Km and product distributions determined by GC-MS) resulting from changes at the C3-position in which the 3β-OH was replaced by 3α-OH, 3β-acetyl, 3-oxo, 3-OMe, 3β-F, 3β-NH2 (protonated species) or 3H group revealed that lanosterol and five substrate analogs were catalyzed and yielded identical side chain products whereas neither the 3H- or 3α-OH lanosterol derivatives were productively bound. Taken together, our results demonstrate a chemical complementarity involving hydrogen bonding formation of specific active site contacts to the nucleophilic C3-group of sterol is required for proper orientation of the substrate C-methyl intermediate in the activated complex.
EFFECT ON ERGOSTEROL BIOSYNTHESIS OF A FUNGICIDE, SSF-109, IN BOTRYTIS CINEREA
Shirane, Noboru,Murabayashi, Akira,Masuko, Michio,Uomori, Atsuko,Yoshimura, Yohko,et al.
, p. 2513 - 2520 (2007/10/02)
Treatment of Botrytis cinerea with a novel fungicide SSF-109, (dl)-cis-1-(4-chlorophenyl)-2-(1H-1,2,4-triazol-1-yl)cyclo-heptanol (0.45 μg ml-1), gave five 14α-methyl sterols, 24-methylene-24(25)-dihydrolanosterol, 24-methylene-24(25)-dihydrolanosten-3-one, obtusifoliol, obtusifolione, and 14α-methylfecosterol, together with ergosterol and ergosta-5,8,22-trien-3β-ol.SSF-109 was found to inhibit the biosynthesis of ergosterol at the 14α-demethylation step.
