title: Mechanism-based enzyme inactivators of phytosterol biosynthesis.
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.
authors.affiliation: Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409-1061, USA.
authors.forename: Wenxu
authors.initials: W
authors.lastname: Zhou
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Song
authors.forename: Ragu
authors.initials: R
authors.lastname: Kanagasabai
authors.forename: Jialin
authors.initials: J
authors.lastname: Liu
authors.forename: Pruthvi
authors.initials: P
authors.lastname: Jayasimha
authors.forename: Archana
authors.initials: A
authors.lastname: Sinha
authors.forename: Phani
authors.initials: P
authors.lastname: Veeramachanemi
authors.forename: Mathew B
authors.initials: MB
authors.lastname: Miller
authors.forename: W David
authors.initials: WD
authors.lastname: Nes
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D002462:Cell Membrane / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008968:Molecular Conformation; D015394:Molecular Structure; D010840:Phytosterols / Q000096:biosynthesis* / Q000737:chemistry; D010940:Plant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D007527:Isoenzymes; D010840:Phytosterols; D010940:Plant Proteins; D008780:Methyltransferases