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3wcm

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Current revision (08:44, 20 March 2024) (edit) (undo)
 
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<StructureSection load='3wcm' size='340' side='right'caption='[[3wcm]], [[Resolution|resolution]] 2.06&Aring;' scene=''>
<StructureSection load='3wcm' size='340' side='right'caption='[[3wcm]], [[Resolution|resolution]] 2.06&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3wcm]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WCM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WCM FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3wcm]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WCM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WCM FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ER4:(3R)-3-{[2-BENZYL-6-(3-METHOXYPROPOXY)PYRIDIN-3-YL]ETHYNYL}-1-AZABICYCLO[2.2.2]OCTAN-3-OL'>ER4</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.06&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3wc9|3wc9]], [[3wca|3wca]], [[3wcb|3wcb]], [[3wcc|3wcc]], [[3wcd|3wcd]], [[3wce|3wce]], [[3wcf|3wcf]], [[3wcg|3wcg]], [[3wch|3wch]], [[3wci|3wci]], [[3wcj|3wcj]], [[3wcl|3wcl]]</div></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ER4:(3R)-3-{[2-BENZYL-6-(3-METHOXYPROPOXY)PYRIDIN-3-YL]ETHYNYL}-1-AZABICYCLO[2.2.2]OCTAN-3-OL'>ER4</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FDFT1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Squalene_synthase Squalene synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.21 2.5.1.21] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3wcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wcm OCA], [https://pdbe.org/3wcm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wcm RCSB], [https://www.ebi.ac.uk/pdbsum/3wcm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wcm 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=3wcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wcm OCA], [https://pdbe.org/3wcm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wcm RCSB], [https://www.ebi.ac.uk/pdbsum/3wcm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wcm ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/FDFT_HUMAN FDFT_HUMAN]
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Trypanosomatid parasites are the causative agents of many neglected tropical diseases and there is currently considerable interest in targeting endogenous sterol biosynthesis in these organisms as a route to the development of novel anti-infective drugs. Here, we report the first x-ray crystallographic structures of the enzyme squalene synthase (SQS) from a trypanosomatid parasite, Trypanosoma cruzi, the causative agent of Chagas disease. We obtained five structures of T. cruzi SQS and eight structures of human SQS with four classes of inhibitors: the substrate-analog S-thiolo-farnesyl diphosphate, the quinuclidines E5700 and ER119884, several lipophilic bisphosphonates, and the thiocyanate WC-9, with the structures of the two very potent quinuclidines suggesting strategies for selective inhibitor development. We also show that the lipophilic bisphosphonates have low nM activity against T. cruzi and inhibit endogenous sterol biosynthesis and that E5700 acts synergistically with the azole drug, posaconazole. The determination of the structures of trypanosomatid and human SQS enzymes with a diverse set of inhibitors active in cells provides insights into SQS inhibition, of interest in the context of the development of drugs against Chagas disease.
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Squalene synthase as a target for Chagas disease therapeutics.,Shang N, Li Q, Ko TP, Chan HC, Li J, Zheng Y, Huang CH, Ren F, Chen CC, Zhu Z, Galizzi M, Li ZH, Rodrigues-Poveda CA, Gonzalez-Pacanowska D, Veiga-Santos P, de Carvalho TM, de Souza W, Urbina JA, Wang AH, Docampo R, Li K, Liu YL, Oldfield E, Guo RT PLoS Pathog. 2014 May 1;10(5):e1004114. doi: 10.1371/journal.ppat.1004114., eCollection 2014 May. PMID:24789335<ref>PMID:24789335</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3wcm" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
*[[Squalene synthase|Squalene synthase]]
*[[Squalene synthase|Squalene synthase]]
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Squalene synthase]]
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[[Category: Chan HC]]
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[[Category: Chan, H C]]
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[[Category: Chen CC]]
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[[Category: Chen, C C]]
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[[Category: Guo RT]]
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[[Category: Guo, R T]]
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[[Category: Huang CH]]
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[[Category: Huang, C H]]
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[[Category: Ko TP]]
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[[Category: Ko, T P]]
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[[Category: Li Q]]
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[[Category: Li, Q]]
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[[Category: Ren F]]
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[[Category: Ren, F]]
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[[Category: Shang N]]
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[[Category: Shang, N]]
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[[Category: Zheng Y]]
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[[Category: Zheng, Y]]
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[[Category: Zhu Z]]
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[[Category: Zhu, Z]]
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[[Category: Drug discovery]]
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[[Category: Er119884]]
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[[Category: Human squalene synthase]]
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[[Category: Isoprenoid]]
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[[Category: Transferase]]
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Current revision

The complex structure of HsSQS wtih ligand, ER119884

PDB ID 3wcm

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