Protein farnesyltransferase inhibitors interfere with farnesyl diphosphate binding by rubber transferase

Christopher J.D. Mau, Sylvie Garneau, Andrew A. Scholte, Jennifer E. Van Fleet, John C. Vederas, Katrina Cornish

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Rubber transferase, a cis-prenyltransferase, catalyzes the addition of thousands of isopentenyl diphosphate (IPP) molecules to an allylic diphosphate initiator, such as farnesyl diphosphate (FPP, 1), in the presence of a divalent metal cofactor. In an effort to characterize the catalytic site of rubber transferase, the effects of two types of protein farnesyltransferase inhibitors, several chaetomellic acid A analogs (2, 4-7) and α -hydroxyfarnesylphosphonic acid (3), on the ability of rubber transferase to add IPP to the allytic diphosphate initiator were determined. Both types of compounds inhibited the activity of rubber transferases from Hevea brasiliensis and Parthenium argentatum, but there were species-specific differences in the inhibition of rubber transferases by these compounds. Several shorter analogs of chaetomellic acid A did not inhibit rubber transferase activity, even though the analogs contained chemical features that are present in an elongating rubber molecule. These results indicate that the initiator-binding site in rubber transferase shares similar features to FPP binding sites in other enzymes.

Original languageEnglish
Pages (from-to)3939-3945
Number of pages7
JournalEuropean Journal of Biochemistry
Issue number19
StatePublished - Oct 2003


  • Chaetomellic acid A
  • Hevea brasiliensis
  • Hydroxyfarnesylphosphonic acid
  • Parthenium argentatum

ASJC Scopus subject areas

  • Biochemistry


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