3e32: Difference between revisions

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<StructureSection load='3e32' size='340' side='right'caption='[[3e32]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
<StructureSection load='3e32' size='340' side='right'caption='[[3e32]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3e32]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E32 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E32 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3e32]] 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=3E32 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E32 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ED2:N-BENZYL-N-(2-{(4-CYANOPHENYL)[(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]AMINO}ETHYL)-1-METHYL-1H-IMIDAZOLE-4-SULFONAMIDE'>ED2</scene>, <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.45&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1d8d|1d8d]], [[1sa5|1sa5]], [[1sa4|1sa4]], [[1kzo|1kzo]], [[2iej|2iej]], [[1kzp|1kzp]], [[3e30|3e30]], [[3e33|3e33]], [[3e34|3e34]], [[3e37|3e37]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ED2:N-BENZYL-N-(2-{(4-CYANOPHENYL)[(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]AMINO}ETHYL)-1-METHYL-1H-IMIDAZOLE-4-SULFONAMIDE'>ED2</scene>, <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Fnta ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Fntb ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Protein_farnesyltransferase Protein farnesyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.58 2.5.1.58] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3e32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e32 OCA], [https://pdbe.org/3e32 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e32 RCSB], [https://www.ebi.ac.uk/pdbsum/3e32 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e32 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3e32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e32 OCA], [https://pdbe.org/3e32 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e32 RCSB], [https://www.ebi.ac.uk/pdbsum/3e32 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e32 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[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). [[https://www.uniprot.org/uniprot/FNTB_RAT FNTB_RAT]] Catalyzes the transfer of a farnesyl moiety from farnesyl pyrophosphate to a cysteine at the fourth position from the C-terminus of several proteins. The beta subunit is responsible for peptide-binding.  
[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]]
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</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=3e32 ConSurf].
</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=3e32 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.
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>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3e32" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Farnesyltransferase 3D structures|Farnesyltransferase 3D structures]]
*[[Farnesyltransferase 3D structures|Farnesyltransferase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Buffalo rat]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Protein farnesyltransferase]]
[[Category: Rattus norvegicus]]
[[Category: Beese, L S]]
[[Category: Beese LS]]
[[Category: Hast, M A]]
[[Category: Hast MA]]
[[Category: Antimalarial]]
[[Category: Ethylenediamine]]
[[Category: Falciparum]]
[[Category: Farnesyltransferase]]
[[Category: Ftase]]
[[Category: Inhibitor]]
[[Category: Malaria]]
[[Category: Metal-binding]]
[[Category: Phosphoprotein]]
[[Category: Plasmodium]]
[[Category: Prenyltransferase]]
[[Category: Transferase]]
[[Category: Zinc]]

Latest revision as of 09:44, 21 February 2024

Protein farnesyltransferase complexed with FPP and ethylenediamine scaffold inhibitor 2

3e32, resolution 2.45Å

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