View source for 4nev


==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]] 2.50&Aring;' 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]] 2.5&#8491;</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&reg;/PubMed&reg;, 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/>
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</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]]