Inhibition of purified p21ras farnesyl:protein transferase by Cys-AAX tetrapeptides

Cell. 1990 Jul 13;62(1):81-8. doi: 10.1016/0092-8674(90)90242-7.


We report the identification, purification, and characterization of a farnesyl:protein transferase that transfers the farnesyl moiety from farnesyl pyrophosphate to a cysteine in p21ras proteins. The enzyme was purified approximately 60,000-fold from rat brain cytosol through use of a chromatography step based on the enzyme's ability to bind to a hexapeptide containing the consensus sequence (Cys-AAX) for farnesylation. The purified enzyme migrated on gel filtration chromatography with an apparent molecular weight of 70,000-100,000. High resolution SDS-polyacrylamide gels showed two closely spaced approximately 50 kd protein bands in the final preparation. The enzyme was inhibited competitively by peptides as short as 4 residues that contained the Cys-AAX motif. These peptides acted as alternative substrates that competed with p21H-ras for farnesylation. Effective peptides included the COOH-terminal sequences of all known p21ras proteins as well as those of lamin A and B.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkyl and Aryl Transferases*
  • Amino Acid Sequence
  • Animals
  • Brain / enzymology*
  • Chromatography, Affinity
  • Chromatography, Gel
  • Chromatography, Ion Exchange
  • Kinetics
  • Male
  • Molecular Sequence Data
  • Oligopeptides / pharmacology*
  • Polyisoprenyl Phosphates / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins p21(ras)
  • Rats
  • Rats, Inbred Strains
  • Sesquiterpenes
  • Structure-Activity Relationship
  • Transferases / antagonists & inhibitors*
  • Transferases / isolation & purification


  • Oligopeptides
  • Polyisoprenyl Phosphates
  • Proto-Oncogene Proteins
  • Sesquiterpenes
  • farnesyl pyrophosphate
  • Transferases
  • Alkyl and Aryl Transferases
  • p21(ras) farnesyl-protein transferase
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins p21(ras)