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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Review
MeSH terms
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Binding Sites
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Catalysis
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Cell Membrane / chemistry
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Enzyme Inhibitors* / chemistry
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Enzyme Inhibitors* / metabolism
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Fungal Proteins* / chemistry
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Fungal Proteins* / genetics
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Fungal Proteins* / metabolism
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Isoenzymes / chemistry
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Methyltransferases* / chemistry
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Methyltransferases* / genetics
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Methyltransferases* / metabolism
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Molecular Conformation
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Molecular Structure
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Phytosterols / biosynthesis*
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Phytosterols / chemistry
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Plant Proteins* / chemistry
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Plant Proteins* / genetics
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Plant Proteins* / metabolism
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Structure-Activity Relationship
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Substrate Specificity
Substances
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Enzyme Inhibitors
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Fungal Proteins
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Isoenzymes
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Phytosterols
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Plant Proteins
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Methyltransferases