View source for 5tqu


==Trypanosoma brucei methionyl-tRNA synthetase in complex with inhibitor==
<StructureSection load='5tqu' size='340' side='right'caption='[[5tqu]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5tqu]] 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=5TQU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TQU 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=I53:2-[2-[[3-(1~{H}-BENZIMIDAZOL-2-YLAMINO)PROPYLAMINO]METHYL]-4,6-BIS(CHLORANYL)INDOL-1-YL]ETHANOL'>I53</scene>, <scene name='pdbligand=MET:METHIONINE'>MET</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=5tqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tqu OCA], [https://pdbe.org/5tqu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tqu RCSB], [https://www.ebi.ac.uk/pdbsum/5tqu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tqu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q38C91_TRYB2 Q38C91_TRYB2] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human African trypanosomiasis is a neglected tropical disease that is lethal if left untreated. Existing therapeutics have limited efficacy and severe associated toxicities. 2-(2-(((3-((1H-Benzo[d]imidazol-2-yl)amino)propyl)amino)methyl)-4,6-dichloro-1H-i ndol-1-yl)ethan-1-ol (NEU-1053) has recently been identified from a high-throughput screen of &gt;42,000 compounds as a highly potent and fast-acting trypanocidal agent capable of curing a bloodstream infection of Trypanosoma brucei in mice. We have designed a library of analogues to probe the structure-activity relationship and improve the predicted central nervous system (CNS) exposure of NEU-1053. We report the activity of these inhibitors of T. brucei, the efficacy of NEU-1053 in a murine CNS model of infection, and identification of the target of NEU-1053 via X-ray crystallography.

From Cells to Mice to Target: Characterization of NEU-1053 (SB-443342) and Its Analogues for Treatment of Human African Trypanosomiasis.,Devine WG, Diaz-Gonzalez R, Ceballos-Perez G, Rojas D, Satoh T, Tear W, Ranade RM, Barros-Alvarez X, Hol WG, Buckner FS, Navarro M, Pollastri MP ACS Infect Dis. 2017 Mar 10;3(3):225-236. doi: 10.1021/acsinfecdis.6b00202. Epub , 2017 Feb 8. PMID:28110521<ref>PMID:28110521</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5tqu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma brucei brucei TREU927]]
[[Category: Barros-Alvarez X]]
[[Category: Hol WGJ]]