3e34
From Proteopedia
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==Protein farnesyltransferase complexed with FPP and ethylenediamine-scaffold inhibitor 10== | ==Protein farnesyltransferase complexed with FPP and ethylenediamine-scaffold inhibitor 10== | ||
| - | <StructureSection load='3e34' size='340' side='right' caption='[[3e34]], [[Resolution|resolution]] 2.05Å' scene=''> | + | <StructureSection load='3e34' size='340' side='right'caption='[[3e34]], [[Resolution|resolution]] 2.05Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[3e34]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[3e34]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E34 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E34 FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ED1:3-{2-[{[1-(TERT-BUTOXYCARBONYL)PIPERIDIN-4-YL]METHYL}(2-{(4-CYANOPHENYL)[(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]AMINO}ETHYL)SULFAMOYL]BIPHENYL-3-YL}PROPANOIC+ACID'>ED1</scene>, <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ED1:3-{2-[{[1-(TERT-BUTOXYCARBONYL)PIPERIDIN-4-YL]METHYL}(2-{(4-CYANOPHENYL)[(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]AMINO}ETHYL)SULFAMOYL]BIPHENYL-3-YL}PROPANOIC+ACID'>ED1</scene>, <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |
| - | <tr | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3e34 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e34 OCA], [https://pdbe.org/3e34 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e34 RCSB], [https://www.ebi.ac.uk/pdbsum/3e34 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e34 ProSAT]</span></td></tr> |
| - | + | </table> | |
| - | + | == Function == | |
| - | <table> | + | [https://www.uniprot.org/uniprot/FNTA_RAT FNTA_RAT] Catalyzes the transfer of a farnesyl or geranyl-geranyl moiety from farnesyl or geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. The alpha subunit is thought to participate in a stable complex with the substrate. The beta subunit binds the peptide substrate. Through RAC1 prenylation and activation may positively regulate neuromuscular junction development downstream of MUSK (By similarity). |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e3/3e34_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e3/3e34_consurf.spt"</scriptWhenChecked> |
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/ | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3e34 ConSurf]. |
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Protein farnesyltransferase (FTase) catalyzes an essential posttranslational lipid modification of more than 60 proteins involved in intracellular signal transduction networks. FTase inhibitors have emerged as a significant target for development of anticancer therapeutics and, more recently, for the treatment of parasitic diseases caused by protozoan pathogens, including malaria (Plasmodium falciparum). We present the X-ray crystallographic structures of complexes of mammalian FTase with five inhibitors based on an ethylenediamine scaffold, two of which exhibit over 1000-fold selective inhibition of P. falciparum FTase. These structures reveal the dominant determinants in both the inhibitor and enzyme that control binding and selectivity. Comparison to a homology model constructed for the P. falciparum FTase suggests opportunities for further improving selectivity of a new generation of antimalarial inhibitors. | ||
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| - | Structural basis for binding and selectivity of antimalarial and anticancer ethylenediamine inhibitors to protein farnesyltransferase.,Hast MA, Fletcher S, Cummings CG, Pusateri EE, Blaskovich MA, Rivas K, Gelb MH, Van Voorhis WC, Sebti SM, Hamilton AD, Beese LS Chem Biol. 2009 Feb 27;16(2):181-92. PMID:19246009<ref>PMID:19246009</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
==See Also== | ==See Also== | ||
| - | *[[Farnesyltransferase|Farnesyltransferase]] | + | *[[Farnesyltransferase 3D structures|Farnesyltransferase 3D structures]] |
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Large Structures]] |
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
| - | [[Category: Beese | + | [[Category: Beese LS]] |
| - | [[Category: Hast | + | [[Category: Hast MA]] |
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Current revision
Protein farnesyltransferase complexed with FPP and ethylenediamine-scaffold inhibitor 10
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