4new: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4new]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NEW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NEW FirstGlance]. <br> | <table><tr><td colspan='2'>[[4new]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NEW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NEW FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2JR:5-{5-[1-(PYRROLIDIN-1-YL)CYCLOHEXYL]-1,3-THIAZOL-2-YL}-1H-INDOLE'>2JR</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2JR:5-{5-[1-(PYRROLIDIN-1-YL)CYCLOHEXYL]-1,3-THIAZOL-2-YL}-1H-INDOLE'>2JR</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nev|4nev]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nev|4nev]]</td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4new FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4new OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4new RCSB], [http://www.ebi.ac.uk/pdbsum/4new PDBsum]</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=4new FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4new OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4new RCSB], [http://www.ebi.ac.uk/pdbsum/4new PDBsum]</span></td></tr> | ||
<table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bryson, S | [[Category: Bryson, S]] | ||
[[Category: Diederich, F | [[Category: Diederich, F]] | ||
[[Category: Krauth-Siegel, R L | [[Category: Krauth-Siegel, R L]] | ||
[[Category: Pai, E F | [[Category: Pai, E F]] | ||
[[Category: Persch, E | [[Category: Persch, E]] | ||
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | ||
[[Category: Reductase]] | [[Category: Reductase]] | ||
Revision as of 17:48, 5 January 2015
Crystal structure of Trypanothione Reductase from Trypanosoma cruzi in complex with inhibitor EP127 (5-{5-[1-(PYRROLIDIN-1-YL)CYCLOHEXYL]-1,3-THIAZOL-2-YL}-1H-INDOLE)Crystal structure of Trypanothione Reductase from Trypanosoma cruzi in complex with inhibitor EP127 (5-{5-[1-(PYRROLIDIN-1-YL)CYCLOHEXYL]-1,3-THIAZOL-2-YL}-1H-INDOLE)
Structural highlights
Publication Abstract from PubMedThe causative agents of the parasitic disease human African trypanosomiasis belong to the family of trypanosomatids. These parasitic protozoa exhibit a unique thiol redox metabolism that is based on the flavoenzyme trypanothione reductase (TR). TR was identified as a potential drug target and features a large active site that allows a multitude of possible ligand orientations, which renders rational structure-based inhibitor design highly challenging. Herein we describe the synthesis, binding properties, and kinetic analysis of a new series of small-molecule inhibitors of TR. The conjunction of biological activities, mutation studies, and virtual ligand docking simulations led to the prediction of a binding mode that was confirmed by crystal structure analysis. The crystal structures revealed that the ligands bind to the hydrophobic wall of the so-called "mepacrine binding site". The binding conformation and potency of the inhibitors varied for TR from Trypanosoma brucei and T. cruzi. Binding to Large Enzyme Pockets: Small-Molecule Inhibitors of Trypanothione Reductase.,Persch E, Bryson S, Todoroff NK, Eberle C, Thelemann J, Dirdjaja N, Kaiser M, Weber M, Derbani H, Brun R, Schneider G, Pai EF, Krauth-Siegel RL, Diederich F ChemMedChem. 2014 Apr 30. doi: 10.1002/cmdc.201402032. PMID:24788386[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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