Sterol C24-methyltransferase: mechanistic studies of the C-methylation reaction with 24-fluorocycloartenol.
The mechanism of the C-methylation reaction was studied with the allylic substrate analog 24-fluorocycloartenol 10 assayed with soybean sterol C24-methyltransferase (SMT). 10 is an effective competitive inhibitor (Ki = 32 microM) of the SMT, and the electron-withdrawing alpha-fluorine substituent was shown to suppress the rate of the C-methylation reaction by one order of magnitude relative to the natural cycloartenol substrate, kcat = 0.02 min(-1) versus 0.6 min(-1); alternately 10 can prevent the critical hydride shift of H24 to C25 to afford time-dependent inactivation of SMT (k(inact) = 0.32 min(-1)).
Wang
Junqing
J
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA.
Liu
Jialin
J
Song
Zhihong
Z
Nes
W David
WD
D001667:Binding, Competitive; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008745:Methylation; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D010840:Phytosterols / Q000737:chemistry / Q000378:metabolism*; D013025:Glycine max / Q000201:enzymology; D014315:Triterpenes / Q000737:chemistry / Q000378:metabolism*
D006845:Hydrocarbons, Fluorinated; D010840:Phytosterols; D014315:Triterpenes; D008780:Methyltransferases; C022670:delta 24-sterol methyltransferase; C100089:cycloartenol