Farnesyltranstransferase
| Farnesyltranstransferase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 2.5.1.29 | ||||||||
| CAS no. | 9032-58-0 | ||||||||
| Databases | |||||||||
| BRENDA | enzyme data | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | enzyme entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| Rhea | reactions | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
Farnesyltranstransferase (EC 2.5.1.29) is an enzyme characterised from pig liver that catalyzes a chemical reaction in the biosynthesis of the diterpenoid alcohol, geranylgeraniol, via its pyrophosphate derivative. The two substrates of the enzyme are farnesyl pyrophosphate and isopentenyl pyrophosphate. These combine to give geranylgeranyl pyrophosphate, with pyrophosphate (PPi) as a byproduct.[1]
This enzyme belongs to the family of transferases, specifically those transferring aryl or alkyl groups other than methyl groups. The systematic name of this enzyme class is trans,trans-farnesyl-diphosphate:isopentenyl-diphosphate farnesyltranstransferase. Other names in common use include geranylgeranyl-diphosphate synthase, geranylgeranyl pyrophosphate synthetase, geranylgeranyl-PP synthetase, farnesyltransferase, and geranylgeranyl pyrophosphate synthase.[2]
This protein may use the morpheein model of allosteric regulation.[3]
Structural studies
As of late 2007, two structures have been solved for this class of enzymes, with PDB accession codes PDB: 2DH4 and PDB: 2Q80.
Inhibitors
A number of farnesyltranstransferase inhibitors including darlifarnib,[4][5] lonafarnib, and tipifarnib have been evaulated as treatments of cancer and other indications.[6]
References
- ↑ Sagami H, Ishi K, Ogura K (1981). "Occurrence and unusual properties of geranylgeranyl pyrophosphate synthetase of pig liver". Biochem. Int. 3: 669–675.
- ↑ Enzyme 2.5.1.29 at KEGG Pathway Database.
- ↑ Selwood T, Jaffe EK (March 2012). "Dynamic dissociating homo-oligomers and the control of protein function". Archives of Biochemistry and Biophysics. 519 (2): 131–143. doi:10.1016/j.abb.2011.11.020. PMC 3298769. PMID 22182754.
- ↑ Patel HV, Smith AE, Chan S, Gasendo JG, Jombik A, Greer JE, et al. (May 2026). "The Farnesyl Transferase Inhibitor Darlifarnib (KO-2806) Resensitizes Relapsing Tumors to RAS Inhibition". Cancer Research. 86 (9): 2273–2285. doi:10.1158/0008-5472.CAN-25-2764. PMC 13136870. PMID 41661652.
- ↑ Gasendo JG, Chan S, Patel HV, Smith AE, Kessler L, Liu YA, et al. (March 2026). "Farnesyl transferase inhibitor KO-2806 (darlifarnib) enhances the anti-tumor activity of tyrosine kinase inhibitors in RCC". Molecular Cancer Therapeutics: OF1–OF11. doi:10.1158/1535-7163.MCT-25-0449. PMID 41881565.
- ↑ Mei LC, Xiao H, Wang DW, Yang GF (March 2026). "Targeting farnesyltransferase for cancer therapy and beyond". Drug Discovery Today. 31 (2) 104622. doi:10.1016/j.drudis.2026.104622. PMID 41672234.