Farnesyltransferase

spinqualitylabelsall models Farnesyltransferaseα subunit (cyan) and β subunit (green) complex with farnesyl diphosphate (FPP) analog, Zn+2 ion (grey), sulfonic acid derivative and CAAX peptide (PDB code 3q75) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Farnesyltransferase (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 . Relevance FTase inhibitors are being tested as anti-cancer and anti-Progeria agents. Structural insights FTase 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. Water molecules are shown as red spheres.

3D structures of farnesyltransferase

Updated on 17-March-2019

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• FTase
  • 1ft1 – rFTase – rat
    
  • 3q73 – CnFTase – Cryptococcus neoformans
• FTase binary complex with FPP
  • 1ft2, 1fpp – rFTase + FPP
    
  • 1o1r, 1o1s, 3ksl, 3ksq - rFTase + FPP-analog
    
• FTase binary complex with peptide
  • 1kzp, 1o1t - rFTase + farnesylated peptide
    
  • 2h6f - hFTase + farnesylated peptide
    
  • 2h6g, 2h6h, 2h6i - hFTase α subunit + β subunit (mutant) + farnesylated peptide
    
  • 3q79 - CnFTase + farnesylated peptide
• FTase binary complex with inhibitor
  • 3eu5 – rFTase + biotin-GPP
    
  • 3euv - rFTase α subunit + β subunit (mutant)+ biotin-GPP
    
  • 1n94, 1n95, 1n9a, 1o5m, 1ni1, 1x81, 2bed, 2r2l - rFTase + inhibitor
    
  • 1nl4 - rFTase α subunit (mutant) + β subunit + inhibitor
• FTase ternary complex with FPP and peptide
  • 1d8d, 1tn8 - rFTase + Ras peptide + FPP-analog
    
  • 1kzo - rFTase + farnesylated Ras peptide + FPP
    
  • 1tn7, 3dpy - rFTase + peptide + FPP-analog
    
  • 1jcr, 1jcs - rFTase + tetrapeptide inhibitor + FPP
    
  • 1d8e - rFTase no Zn + Ras peptide + FPP-analog
    
  • 1tn6 - hFTase + Rap2a peptide + FPP-analog
    
  • 3q75, 3q78 - CnFTase + peptide + FPP-analog
    
  • 4l9p - AfFTase + peptide + FPP-analog – Apergillus fumigatus
    
• FTase ternary complex with FPP and inhibitor
  • 1sa5, 3e30, 3e32, 3e33, 3e34, 3e37 - rFTase + inhibitor + FPP
    
  • 4gtm, 4gto, 4gtp, 4gtq, 4gtr - rFTase α subunit + β subunit + inhibitor + FPP
    
  • 2zir, 2zis - rFTase α subunit (mutant) + β subunit + inhibitor + FPP
    
  • 1jcq – hFTase α subunit (mutant) + β subunit + inhibitor + FPP– human
    
  • 1ld7, 1ld8, 1mzc, 1sa4, 1s63, 2f0y - hFTase + inhibitor + FPP
    
  • 2iej - hFTase + inhibitor + FPP-analog
    
  • 3pz4 - FTase + inhibitor + FPP – mouse
    
  • 3q7a, 3q7f - CnFTase + inhibitor + FPP
    
  • 3fsx, 3sfy - CnFTase + inhibitor + FPP-analog
    
  • 3sfx - CnFTase α subunit + β subunit + inhibitor + FPP
    
  • 4lnb, 4lng, 4mbg - AfFTase (mutant) + inhibitor + FPP
    
• FTase ternary complex with GPP and protein
  • 1n4p, 1n4r, 1n4s - rFTase α subunit + GTase β subunit + transforming protein + GPP
    

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Michal Harel, Alexander Berchansky, Joel L. Sussman