View source for 6er5


==X-ray structure of Trypanothione Reductase from Leishmania infantum in complex with 2-(diethylamino)ethyl 4-((3-(4-nitrophenyl)-3-oxopropyl)amino)benzoate==
<StructureSection load='6er5' size='340' side='right'caption='[[6er5]], [[Resolution|resolution]] 3.37&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6er5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_infantum Leishmania infantum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ER5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ER5 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]] 3.37&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BVN:2-(diethylamino)ethyl+4-[[3-(4-nitrophenyl)-3-oxidanylidene-propyl]amino]benzoate'>BVN</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=6er5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6er5 OCA], [https://pdbe.org/6er5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6er5 RCSB], [https://www.ebi.ac.uk/pdbsum/6er5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6er5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A4HSF7_LEIIN A4HSF7_LEIIN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Trypanothione reductase (TR) is considered to be one of the best targets to find new drugs against Leishmaniasis. This enzyme is fundamental for parasite survival in the host since it reduces trypanothione, a molecule used by the tryparedoxin/tryparedoxin peroxidase system of Leishmania to neutralize hydrogen peroxide produced by host macrophages during infection. In order to identify new lead compounds against Leishmania we developed and validated a new luminescence-based high-throughput screening (HTS) assay that allowed us to screen a library of 120,000 compounds. We identified a novel chemical class of TR inhibitors, able to kill parasites with an IC50 in the low micromolar range. The X-ray crystal structure of TR in complex with a compound from this class (compound 3) allowed the identification of its binding site in a pocket at the entrance of the NADPH binding site. Since the binding site of compound 3 identified by the X-ray structure is unique, and is not present in human homologs such as glutathione reductase (hGR), it represents a new target for drug discovery efforts.

Identification and binding mode of a novel Leishmania Trypanothione reductase inhibitor from high throughput screening.,Turcano L, Torrente E, Missineo A, Andreini M, Gramiccia M, Di Muccio T, Genovese I, Fiorillo A, Harper S, Bresciani A, Colotti G, Ilari A PLoS Negl Trop Dis. 2018 Nov 26;12(11):e0006969. doi:, 10.1371/journal.pntd.0006969. eCollection 2018 Nov. PMID:30475811<ref>PMID:30475811</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6er5" style="background-color:#fffaf0;"></div>

==See Also==
*[[Trypanothione reductase|Trypanothione reductase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Leishmania infantum]]
[[Category: Fiorillo A]]
[[Category: Ilari A]]