Sterol methyl transferase: Enzymology and inhibition

W. David Nes

Research output: Contribution to journalReview articlepeer-review

114 Scopus citations


Sterol C-methylations catalyzed by the (S)-adenosyl-L-methionine: Δ24-sterol methyl transferase (SMT) have provided the focus for study of electrophilic alkylations, a reaction type of functional importance in C-C bond formation of natural products. SMTs occur generally in nature, but do not occur in animal systems, suggesting that the difference in sterol synthetic pathways can be exploited therapeutically and in insect-plant interactions. The SMT genes from several plants and fungi have been cloned, sequenced and expressed in bacteria or yeast and bioengineered into tobacco or tomato plants. These enzymes share significant amino acid sequence similarity in the putative sterol and AdoMet binding sites. Investigations of the molecular recognition of sterol fitness and studies with stereospecifically labeled substrates as well as various sterol analogs assayed with native or mutant SMTs from fungi and plants have been carried out recently in our own and other laboratories. These analyses have led to an active-site model, referred to as the 'steric-electric plug' model, which is consistent with a non-covalent mechanism involving the intermediacy of a 24β-methyl (or ethyl) sterol bound to the ternary complex. Despite the seeming differences between fungal and plant SMT activities the recent data indicate that a distinct SMT or family of SMTs exist in these organisms which bind and transform sterols according to a similar mechanistic plan. Vascular plants have been found to express different complements of C1/C2-activities in the form of at least three SMT isoforms. This enzyme multiplicity can be a target of regulatory control to affect phytosterol homeostasis in transgenic plants. The state of our current understanding of SMT enzymology and inhibition is presented. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)63-88
Number of pages26
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Issue number1-3
StatePublished - Dec 15 2000


  • Bioengineering phytosterol synthesis
  • C-Methyl transfer mechanism
  • Ergosterol
  • Inhibitor
  • Kinetic isotope effect
  • Site-directed mutagenesis
  • Sterol methyl transferase


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