Sterol C24-methyltransferase: Mechanistic studies of the C-methylation reaction with 24-fluorocycloartenol

Junqing Wang, Jialin Liu, Zhihong Song, W. David Nes

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8 Scopus citations

Abstract

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 μM) of the SMT, and the electron-withdrawing α-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 (kinact = 0.32 min-1).

Original languageEnglish
Pages (from-to)232-235
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2008

Keywords

  • 24-Fluorocycloartenol
  • Mechanism-based inactivator
  • Sterol C24-methyltransferase
  • Suicide substrate

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