6btl
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Trypanothione Reductase from Trypanosoma brucei in complex with inhibitor RD117 1-[2-(Piperazin-1-yl)ethyl]-5-{5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl}-1H-indole== | |
| + | <StructureSection load='6btl' size='340' side='right' caption='[[6btl]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6btl]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BTL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BTL FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RD7:1-[2-(piperazin-1-yl)ethyl]-5-{5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl}-1H-indole'>RD7</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nev|4nev]]</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Trypanothione-disulfide_reductase Trypanothione-disulfide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.12 1.8.1.12] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6btl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6btl OCA], [http://pdbe.org/6btl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6btl RCSB], [http://www.ebi.ac.uk/pdbsum/6btl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6btl ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The tropical diseases human African trypanosomiasis, Chagas disease, and the various forms of leishmaniasis are caused by parasites of the family of trypanosomatids. These protozoa possess a unique redox metabolism based on trypanothione and trypanothione reductase (TR), making TR a promising drug target. We report the optimization of properties and potency of cyclohexylpyrrolidine inhibitors of TR by structure-based design. The best inhibitors were freely soluble and showed competitive inhibition constants (Ki ) against Trypanosoma (T.) brucei TR and T. cruzi TR and in vitro activities (half-maximal inhibitory concentration, IC50 ) against these parasites in the low micromolar range, with high selectivity against human glutathione reductase. X-ray co-crystal structures confirmed the binding of the ligands to the hydrophobic wall of the "mepacrine binding site" with the new, solubility-providing vectors oriented toward the surface of the large active site. | ||
| - | + | Biological Evaluation and X-ray Co-crystal Structures of Cyclohexylpyrrolidine Ligands for Trypanothione Reductase, an Enzyme from the Redox Metabolism of Trypanosoma.,De Gasparo R, Brodbeck-Persch E, Bryson S, Hentzen NB, Kaiser M, Pai EF, Krauth-Siegel RL, Diederich F ChemMedChem. 2018 May 8;13(9):957-967. doi: 10.1002/cmdc.201800067. Epub 2018 Apr, 6. PMID:29624890<ref>PMID:29624890</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | [[Category: | + | <div class="pdbe-citations 6btl" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Trypanothione-disulfide reductase]] | ||
[[Category: Bryson, S]] | [[Category: Bryson, S]] | ||
| - | [[Category: Krauth-Siegel, R.L]] | ||
[[Category: Diederich, F]] | [[Category: Diederich, F]] | ||
| - | [[Category: | + | [[Category: Gasparo, R De]] |
| + | [[Category: Krauth-Siegel, R L]] | ||
| + | [[Category: Pai, E F]] | ||
| + | [[Category: Complex]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Oxidoreductase-inhibitor complex]] | ||
| + | [[Category: Sleeping sickness]] | ||
Revision as of 05:54, 6 June 2018
Crystal structure of Trypanothione Reductase from Trypanosoma brucei in complex with inhibitor RD117 1-[2-(Piperazin-1-yl)ethyl]-5-{5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl}-1H-indole
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