Farnesyltransferase

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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]]) '>
<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 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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== Relevance ==
== Relevance ==
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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.
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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</StructureSection>
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==3D structures of farnesyltransferase==
==3D structures of farnesyltransferase==
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[[Farnesyltransferase 3D structures]]
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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</StructureSection>
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*FTase
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**[[1ft1]] – rFTase – rat<br />
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**[[3q73]] – CnFTase – ''Cryptococcus neoformans''
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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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**[[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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**[[1n4p]], [[1n4r]], [[1n4s]] - rFTase α subunit + GTase β subunit + transforming protein + GPP<br />
 
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}}
 
== References ==
== References ==
<references/>
<references/>
[[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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