Reaction: farnesyl diphosphate + protein-cysteine = S-farnesyl protein + diphosphate
Other name(s): FTase
Systematic name: farnesyl-diphosphate:protein-cysteine farnesyltransferase
Comments: This enzyme, along with protein geranylgeranyltransferase types I (EC 220.127.116.11) and II (EC 18.104.22.168), constitutes the protein prenyltransferase family of enzymes. Catalyses the formation of a thioether linkage between the C-1 of an isoprenyl group and a cysteine residue fourth from the C-terminus of the protein. These protein acceptors have the C-terminal sequence CA1A2X, where the terminal residue, X, is preferably serine, methionine, alanine or glutamine; leucine makes the protein a substrate for EC 22.214.171.124. The enzymes are relaxed in specificity for A1, but cannot act if A2 is aromatic. Substrates of the prenyltransferases include Ras, Rho, Rab, other Ras-related small GTP-binding proteins, γ-subunits of heterotrimeric G-proteins, nuclear lamins, centromeric proteins and many proteins involved in visual signal transduction. A zinc metalloenzyme that requires Mg2+ for activity.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 131384-38-8
1. Furfine, E.S., Leban, J.J., Landavazo, A., Moomaw, J.F. and Casey, P.J. Protein farnesyltransferase: kinetics of farnesyl pyrophosphate binding and product release. Biochemistry 34 (1995) 6857-6862. [PMID: 7756316]
2. Casey, P.J. and Seabra, M.C. Protein prenyltransferases. J. Biol. Chem. 271 (1996) 5289-5292. [PMID: 8621375]
3. Long, S.B., CASey, P.J. and Beese, L.S. Cocrystal structure of protein farnesyltransferase complexed with a farnesyl diphosphate substrate. Biochemistry 37 (1998) 9612-9618. [PMID: 9657673]
4. Micali, E., Chehade, K.A., Isaacs, R.J., Andres, D.A. and Spielmann, H.P. Protein farnesyltransferase isoprenoid substrate discrimination is dependent on isoprene double bonds and branched methyl groups. Biochemistry 40 (2001) 12254-12265. [PMID: 11591144]
5. Long, S.B., CASey, P.J. and Beese, L.S. Reaction path of protein farnesyltransferase at atomic resolution. Nature 419 (2002) 645-650. [PMID: 12374986]
6. Gibbs, R.A. Prenyl transfer and the enzymes of terpenoid and steroid biosynthesis. In: Sinnott, M. (Ed.), Comprehensive Biological Catalysis. A Mechanistic Reference., vol. 1, Academic Press, San Diego, CA, 1998, pp. 31-118.