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ID: ALA1131730

Journal: Bioorg Med Chem Lett

Title: Isolation and characterization of an active-site peptide from a sterol methyl transferase with a mechanism-based inhibitor.

Authors: Marshall JA, Nes WD.

Abstract: Chemical affinity labeling of pure sterol methyl transferase (SMT) from Saccharomyces cerevisiae using the mechanism-based irreversible inhibitor, [3-3H]26,27-dehydrozymosterol, inhibited the SMT with an apparent Ki of 1.1 microM and k(inact) of 1.52 min(-1). The protein-inhibitor adduct was subjected to cleavage with trypsin and the resulting covalently modified peptide was analyzed by Edman sequencing from the N-terminus. The radiochemically labeled ca. 5.0 kDa peptide fragment of the cleavage mixture was shown to be contiguous through 17 residues to a segment that includes a highly conserved hydrophobic motif (Region I, stretching between T78 and F91) characteristic of SMT enzymes. The results confirm that Region I is the sterol binding/active site.

CiteXplore: 10386930

DOI: 10.1016/s0960-894x(99)00242-5