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Inhibition of C-terminal O-methyltransferase by a rat liver cytosolic peptide


The activity of S-famesylcysteine O-methyltransferase was assayed by incubating the enzyme with a syntheticin vitro substrate, [N-acetyl-S-trans, trans-famesyl-L-cysteine (AFC)], together with S-adenosyl-L-[methyl-14C]methionine. The resulting methylesterification product, [N-acetyl-S-trans, trans-famesyl-L-cysteine (methyl-14C) ester (AFCME)], was then analyzed either directly on HPLC or by converting the AFC[methyl-14C]ME to [methyl-14C] alcohol by basehydrolysis. Employing these two analytical methods, it was established that a peptide purified from rat liver cytosol fraction [Int. J. Biochem., 25, 1157 (1993)] strongly inhibited the above enzyme activity with IC50 of 7.1X10−8 M. Also, the S-famesylcysteine O-methyltransferase from several human colon cancer cells was also equally inhibited by the peptide.

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Correspondence to Seung Hee Park or Hyang Woo Lee.

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Park, S.H., Lee, H.W. Inhibition of C-terminal O-methyltransferase by a rat liver cytosolic peptide. Arch. Pharm. Res. 17, 354 (1994).

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Key words

  • Peptide inhibitor
  • S-famesylcysteine O-methyltransferase