3wcf: Difference between revisions
No edit summary |
No edit summary |
||
| (One intermediate revision by the same user not shown) | |||
| Line 1: | Line 1: | ||
==The complex structure of HsSQS wtih ligand,BPH1218== | ==The complex structure of HsSQS wtih ligand,BPH1218== | ||
<StructureSection load='3wcf' size='340' side='right' caption='[[3wcf]], [[Resolution|resolution]] 2.22Å' scene=''> | <StructureSection load='3wcf' size='340' side='right'caption='[[3wcf]], [[Resolution|resolution]] 2.22Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3wcf]] is a 6 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3wcf]] 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=3WCF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WCF FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.22Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BH8:HYDROGEN+[(1S)-2-(3-DECYL-1H-IMIDAZOL-3-IUM-1-YL)-1-PHOSPHONOETHYL]PHOSPHONATE'>BH8</scene></td></tr> | |||
<tr id=' | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3wcf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wcf OCA], [https://pdbe.org/3wcf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wcf RCSB], [https://www.ebi.ac.uk/pdbsum/3wcf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wcf 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/FDFT_HUMAN FDFT_HUMAN] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 26: | Line 26: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Chan | [[Category: Chan HC]] | ||
[[Category: Chen | [[Category: Chen CC]] | ||
[[Category: Guo | [[Category: Guo RT]] | ||
[[Category: Huang | [[Category: Huang CH]] | ||
[[Category: Ko | [[Category: Ko TP]] | ||
[[Category: Li | [[Category: Li Q]] | ||
[[Category: Ren | [[Category: Ren F]] | ||
[[Category: Shang | [[Category: Shang N]] | ||
[[Category: Zheng | [[Category: Zheng Y]] | ||
[[Category: Zhu | [[Category: Zhu Z]] | ||
Latest revision as of 16:03, 8 November 2023
The complex structure of HsSQS wtih ligand,BPH1218The complex structure of HsSQS wtih ligand,BPH1218
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
|
| ||||||||||||||||||