3wcc: Difference between revisions
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==The complex structure of TcSQS with ligand, E5700== | ==The complex structure of TcSQS with ligand, E5700== | ||
<StructureSection load='3wcc' size='340' side='right' caption='[[3wcc]], [[Resolution|resolution]] 2.32Å' scene=''> | <StructureSection load='3wcc' size='340' side='right'caption='[[3wcc]], [[Resolution|resolution]] 2.32Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3wcc]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WCC OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[3wcc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_cruzi_strain_CL_Brener Trypanosoma cruzi strain CL Brener]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WCC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WCC FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E5S:(3R)-3-({2-BENZYL-6-[(3R,4S)-3-HYDROXY-4-METHOXYPYRROLIDIN-1-YL]PYRIDIN-3-YL}ETHYNYL)-1-AZABICYCLO[2.2.2]OCTAN-3-OL'>E5S</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]] 2.32Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E5S:(3R)-3-({2-BENZYL-6-[(3R,4S)-3-HYDROXY-4-METHOXYPYRROLIDIN-1-YL]PYRIDIN-3-YL}ETHYNYL)-1-AZABICYCLO[2.2.2]OCTAN-3-OL'>E5S</scene></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=3wcc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wcc OCA], [https://pdbe.org/3wcc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wcc RCSB], [https://www.ebi.ac.uk/pdbsum/3wcc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wcc ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q4CWB4_TRYCC Q4CWB4_TRYCC] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 16: | Line 18: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3wcc" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Squalene synthase|Squalene synthase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Chan | [[Category: Trypanosoma cruzi strain CL Brener]] | ||
[[Category: Chen | [[Category: Chan HC]] | ||
[[Category: Guo | [[Category: Chen CC]] | ||
[[Category: Huang | [[Category: Guo RT]] | ||
[[Category: Ko | [[Category: Huang CH]] | ||
[[Category: Li | [[Category: Ko TP]] | ||
[[Category: Ren | [[Category: Li Q]] | ||
[[Category: Shang | [[Category: Ren F]] | ||
[[Category: Zheng | [[Category: Shang N]] | ||
[[Category: Zhu | [[Category: Zheng Y]] | ||
[[Category: Zhu Z]] | |||
Latest revision as of 16:03, 8 November 2023
The complex structure of TcSQS with ligand, E5700The complex structure of TcSQS with ligand, E5700
Structural highlights
FunctionPublication Abstract from PubMedTrypanosomatid 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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