Farnesyltransferase
From Proteopedia
FunctionFarnesyltransferase (FTase) is part of the prenyltransferase group. FTase modifies proteins by adding farnesyl diphosphate (FPP) – an isoprenoid lipid – to a cysteine in a CAAX motif near the C terminal. This addition forms a thioether linkage, makes the protein more hydrophobic and associates it with the membrane. Farnesylated proteins – like those of the Ras family - are involved in cellular signaling[1]. RelevanceFTase inhibitors are being tested as anti-cancer and anti-Progeria agents. Structural insightsFTase are composed of 2 subunits. α subunit is in cyan, β subunit is in green. CAAX peptide and ligands. The CAAX motif and β subunit coordinate with the Zn+2 ion and the FPP predominantly coordinates with the β subunit[2]. Water molecules are shown as red spheres. 3D structures of farnesyltransferaseFarnesyltransferase 3D structures
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References
- ↑ Reid TS, Terry KL, Casey PJ, Beese LS. Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity. J Mol Biol. 2004 Oct 15;343(2):417-33. PMID:15451670 doi:10.1016/j.jmb.2004.08.056
- ↑ Hast MA, Nichols CB, Armstrong SM, Kelly SM, Hellinga HW, Alspaugh JA, Beese LS. Structures of Cryptococcus neoformans Protein Farnesyltransferase Reveal Strategies for Developing Inhibitors That Target Fungal Pathogens. J Biol Chem. 2011 Oct 7;286(40):35149-62. Epub 2011 Aug 4. PMID:21816822 doi:10.1074/jbc.M111.250506
