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4nev
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 4nev is ON HOLD Authors: Persch, E., Bryson, S., Pai, E.F., Krauth-Siegel, R.L., Diederich, F. Description: Crystal structure of Trypanothione Redu...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Trypanothione Reductase from Trypanosoma brucei in complex with inhibitor EP127 (5-{5-[1-(PYRROLIDIN-1-YL)CYCLOHEXYL]-1,3-THIAZOL-2-YL}-1H-INDOLE)== | |
| + | <StructureSection load='4nev' size='340' side='right'caption='[[4nev]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4nev]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei_TREU927 Trypanosoma brucei brucei TREU927]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NEV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NEV FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2JR:5-{5-[1-(PYRROLIDIN-1-YL)CYCLOHEXYL]-1,3-THIAZOL-2-YL}-1H-INDOLE'>2JR</scene>, <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=SO4:SULFATE+ION'>SO4</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=4nev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nev OCA], [https://pdbe.org/4nev PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nev RCSB], [https://www.ebi.ac.uk/pdbsum/4nev PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nev ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/Q389T8_TRYB2 Q389T8_TRYB2] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The 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<ref>PMID:24788386</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4nev" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Trypanothione reductase|Trypanothione reductase]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Trypanosoma brucei brucei TREU927]] | ||
| + | [[Category: Bryson S]] | ||
| + | [[Category: Diederich F]] | ||
| + | [[Category: Krauth-Siegel RL]] | ||
| + | [[Category: Pai EF]] | ||
| + | [[Category: Persch E]] | ||
Current revision
Crystal structure of Trypanothione Reductase from Trypanosoma brucei in complex with inhibitor EP127 (5-{5-[1-(PYRROLIDIN-1-YL)CYCLOHEXYL]-1,3-THIAZOL-2-YL}-1H-INDOLE)
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