8gcc
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==T. cruzi topoisomerase II alpha bound to dsDNA and the covalent inhibitor CT1== | |
| + | <StructureSection load='8gcc' size='340' side='right'caption='[[8gcc]], [[Resolution|resolution]] 2.94Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8gcc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [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=8GCC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GCC FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.94Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=YWX:2-{3-[(Z)-iminomethyl]-1H-1,2,4-triazol-1-yl}-1-{(3M)-3-[2-(trifluoromethyl)phenyl]-6H-pyrrolo[3,4-b]pyridin-6-yl}ethan-1-one'>YWX</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=8gcc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gcc OCA], [https://pdbe.org/8gcc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gcc RCSB], [https://www.ebi.ac.uk/pdbsum/8gcc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gcc ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/Q4DE53_TRYCC Q4DE53_TRYCC] Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks.[RuleBase:RU362094] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Millions who live in Latin America and sub-Saharan Africa are at risk of trypanosomatid infections, which cause Chagas disease and human African trypanosomiasis (HAT). Improved HAT treatments are available, but Chagas disease therapies rely on two nitroheterocycles, which suffer from lengthy drug regimens and safety concerns that cause frequent treatment discontinuation. We performed phenotypic screening against trypanosomes and identified a class of cyanotriazoles (CTs) with potent trypanocidal activity both in vitro and in mouse models of Chagas disease and HAT. Cryo-electron microscopy approaches confirmed that CT compounds acted through selective, irreversible inhibition of trypanosomal topoisomerase II by stabilizing double-stranded DNA:enzyme cleavage complexes. These findings suggest a potential approach toward successful therapeutics for the treatment of Chagas disease. | ||
| - | + | Cyanotriazoles are selective topoisomerase II poisons that rapidly cure trypanosome infections.,Rao SPS, Gould MK, Noeske J, Saldivia M, Jumani RS, Ng PS, Rene O, Chen YL, Kaiser M, Ritchie R, Francisco AF, Johnson N, Patra D, Cheung H, Deniston C, Schenk AD, Cortopassi WA, Schmidt RS, Wiedemar N, Thomas B, Palkar R, Ghafar NA, Manoharan V, Luu C, Gable JE, Wan KF, Myburgh E, Mottram JC, Barnes W, Walker J, Wartchow C, Aziz N, Osborne C, Wagner J, Sarko C, Kelly JM, Manjunatha UH, Maser P, Jiricek J, Lakshminarayana SB, Barrett MP, Diagana TT Science. 2023 Jun 30;380(6652):1349-1356. doi: 10.1126/science.adh0614. Epub 2023 , Jun 29. PMID:37384702<ref>PMID:37384702</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8gcc" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Escherichia coli]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Trypanosoma cruzi strain CL Brener]] | ||
| + | [[Category: Deniston C]] | ||
| + | [[Category: Noeske J]] | ||
| + | [[Category: Schenk A]] | ||
Revision as of 07:23, 12 July 2023
T. cruzi topoisomerase II alpha bound to dsDNA and the covalent inhibitor CT1
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