Mechanism-based enzyme inactivators of phytosterol biosynthesis

Wenxu Zhou, Zhihong Song, Ragu Kanagasabai, Jialin Liu, Pruthvi Jayasimha, Archana Sinha, Phani Veeramachanemi, Mathew B. Miller, W. David Nes

Research output: Contribution to journalReview article

13 Scopus citations

Abstract

Current progress on the mechanism and substrate recognition by sterol methyl transferase (SMT), the role of mechanism-based inactivators, other inhibitors of SMT action to probe catalysis and phytosterol synthesis is reported. SMT is a membrane-bound enzyme which catalyzes the coupled C-methylation-deprotonation reaction of sterol acceptor molecules generating the 24-alkyl sterol side chains of fungal ergosterol and plant sitosterol. This C-methylation step can be rate-limiting in the post-lanosterol (fungal) or post-cycloartenol (plant) pathways. A series of sterol analogs designed to impair SMT activity irreversibly have provided deep insight into the C-methylation reaction and topography of the SMT active site and as reviewed provide leads for the development of antifungal agents.

Original languageEnglish
Pages (from-to)185-203
Number of pages19
JournalMolecules
Volume9
Issue number4
DOIs
StatePublished - Apr 2004

Keywords

  • Ergosterol
  • Sitosterol
  • Stereochemistry
  • Sterol biosynthesis inhibitors

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