Farnesyltransferase

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{{STRUCTURE_1tn7| PDB=1tn7 | SIZE=400| SCENE= |right|CAPTION=Rat farnesyltransferase α subunit (grey) and β subunit (green) complex with farnesyl diphosphate (FPP) analog, acetate and peptide [[1tn7]] }}
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<StructureSection load='' size='350' side='right' scene='48/485616/Cv/2' caption=' Farnesyltransferase α 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]]) '>
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== Function ==
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'''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<ref>PMID:15451670</ref>.
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'''Farnesyltransferase''' (FTase) is part of the prenyltransferase group. FTase modifies proteins by adding farnesyl diphosphate (FPP) – an isoprenoid lipid – to a cysteine 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. Thus, FTase inhibitors are being tested as anti-cancer agents. FTase are composed of 2 subunits. The β subunit coordinates a Zn atom.
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==3D structures of farnesyltransferase==
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FTase inhibitors are being tested as anti-cancer and anti-Progeria agents.
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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== Structural insights ==
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*FTase
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FTase are composed of 2 subunits. <scene name='48/485616/Cv/11'>α subunit</scene> is in cyan, <scene name='48/485616/Cv/12'>β subunit</scene> is in green. <scene name='48/485616/Cv/13'>CAAX peptide and ligands</scene>. The <scene name='48/485616/Cv/14'>CAAX motif and β subunit coordinate with the Zn+2 ion</scene> and the <scene name='48/485616/Cv/15'>FPP predominantly coordinates with the β subunit</scene><ref>PMID:21816822</ref>. Water molecules are shown as red spheres.
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**[[1ft1]] – rFTase – rat<br />
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==3D structures of farnesyltransferase==
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**[[3q73]] – CnFTase – ''Cryptococcus neoformans''
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[[Farnesyltransferase 3D structures]]
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*FTase binary complex with FPP
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**[[1ft2]], [[1fpp]] – rFTase + FPP<BR />
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**[[1o1r]], [[1o1s]], [[3ksl]], [[3ksq]] - rFTase + FPP-analog<br />
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*FTase binary complex with peptide
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**[[1kzp]], [[1o1t]] - rFTase + farnesylated peptide<br />
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**[[2h6f]] - hFTase + farnesylated peptide<br />
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**[[2h6g]], [[2h6h]], [[2h6i]] - hFTase α subunit + β subunit (mutant) + farnesylated peptide<br />
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**[[3q79]] - CnFTase + farnesylated peptide
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*FTase binary complex with inhibitor
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**[[3eu5]] – rFTase + biotin-GPP<br />
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**[[3euv]] - rFTase α subunit + β subunit (mutant)+ biotin-GPP<br />
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**[[1n94]], [[1n95]], [[1n9a]], [[1o5m]], [[1ni1]], [[1x81]], [[2bed]], [[2r2l]] - rFTase + inhibitor<br />
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**[[1nl4]] - rFTase α subunit (mutant) + β subunit + inhibitor
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*FTase ternary complex with FPP and peptide
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**[[1d8d]], [[1tn8]] - rFTase + Ras peptide + FPP-analog<br />
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**[[1kzo]] - rFTase + farnesylated Ras peptide + FPP<BR />
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**[[1tn7]], [[3dpy]] - rFTase + peptide + FPP-analog<BR />
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**[[1jcr]], [[1jcs]] - rFTase + tetrapeptide inhibitor + FPP<BR />
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**[[1d8e]] - rFTase no Zn + Ras peptide + FPP-analog<br />
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**[[1tn6]] - hFTase + Rap2a peptide + FPP-analog<br />
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**[[3q75]], [[3q78]] - CnFTase + peptide + FPP-analog<br />
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**[[4l9p]] - AfFTase + peptide + FPP-analog – ''Apergillus fumigatus''<br />
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*FTase ternary complex with FPP and inhibitor
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**[[1sa5]], [[3e30]], [[3e32]], [[3e33]], [[3e34]], [[3e37]] - rFTase + inhibitor + FPP<BR />
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</StructureSection>
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**[[4gtm]], [[4gto]], [[4gtp]], [[4gtq]], [[4gtr]] - rFTase α subunit + β subunit + inhibitor + FPP<br />
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**[[2zir]], [[2zis]] - rFTase α subunit (mutant) + β subunit + inhibitor + FPP<BR />
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**[[1jcq]] – hFTase α subunit (mutant) + β subunit + inhibitor + FPP– human<br />
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**[[1ld7]], [[1ld8]], [[1mzc]], [[1sa4]], [[1s63]], [[2f0y]] - hFTase + inhibitor + FPP<BR />
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**[[2iej]] - hFTase + inhibitor + FPP-analog<br />
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**[[3pz4]] - FTase + inhibitor + FPP – mouse<br />
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**[[3q7a]], [[3q7f]] - CnFTase + inhibitor + FPP<BR />
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**[[3fsx]], [[3sfy]] - CnFTase + inhibitor + FPP-analog<br />
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**[[3sfx]] - CnFTase α subunit + β subunit + inhibitor + FPP<br />
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**[[4lnb]], [[4lng]], [[4mbg]] - AfFTase (mutant) + inhibitor + FPP<br />
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*FTase ternary complex with GPP and protein
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== References ==
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<references/>
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**[[1n4p]], [[1n4r]], [[1n4s]] - rFTase α subunit + GTase β subunit + transforming protein + GPP<br />
 
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[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Farnesyltransferase α 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)

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References

  1. ↑ 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
  2. ↑ 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

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

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