Farnesyltransferase



Farnesyltransferase is one of the three FTase inhibitors are undergoing testing as anti-cancer agents. FTase inhibitors have shown efficacy as anti-parasitic agents, as well. FTase is also believed to play an important role in development of progeria and various forms of cancers.

Overview

Farnesyltransferase, cellular signaling wherein membrane association is critical for function.

Farnesyltransferase structure and function

Farnesyltransferase has two magnesium ion on the farnesyl diphosphate, displacing the diphosphate. The product remains bound to farnesyltransferase until displaced by new substrates. The last three amino acids of the CaaX motif are removed later.

Specificity

There are four binding pockets in FTase, which accommodate the last four amino acids on the carboxyl-terminus of a protein. Only those with a suitable CaaX motif can bind. As stated above the fourth-to-last residue is always a cysteine. The other three residues may vary. The carboxyl-terminal amino acid (X) discriminates FTase’s targets from those of the other prenyltransferases, allowing only six different amino acids to bind with any affinity. It has been shown that geranylgeranyltransferase one of the other prenyltransferases can prenylate some of the substrates of Farnesyltransferase and vice versa.

References

  1. Reid, T. Scott, Terry, Kimberly L., Casey, Patrick J., Beese, Lorena S., (2004) Crystallographic Analysis of CaaX prenyltransferases Complexed with Substrates Defines Rules of Protein Substrate Selectivity, J. Mol. Bio, 343, 417-433.
  2. Eastman, Richard T., Buckner, Frederick S., et al., (2006) Fighting parasitic disease by Blocking Protein Farnesylation, Journal of Lipid Research, 47, 233-240.
  3. Beese, Lorena, S., Lane, Kimberly T. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type 1. Journal of Lipid Research, 47, 68 –698.
  4. Long, Stephen B., Casey, Patrick J., Beese, Lorena S., Reaction path of protein farnesyltransferase at atomic resolution. Nature, 419, 645-650.

See also

  • Prenylation
  • Farnesyltransferase inhibitor
  • Geranylgeranyltransferase type 1 - also referred to as Geranylgeranyltranferase 1 or just Geranylgeranyltranferase
  • Rab geranylgeranyltransferase - Geranylgeranyltransferase type 2
v • d • e
Glutathione S-transferase - Farnesyl-diphosphate farnesyltransferase - Spermine synthase - Alkylglycerone phosphate synthase - Farnesyltransferase - Geranylgeranyltransferase type 1 - Porphobilinogen deaminase
 
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