View source for 6gxy


==Tryparedoxin from Trypanosoma brucei in complex with CFT==
<StructureSection load='6gxy' size='340' side='right'caption='[[6gxy]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6gxy]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei Trypanosoma brucei brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GXY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GXY 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]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FFN:5-(4-fluorophenyl)-2-methyl-3~{H}-thieno[2,3-d]pyrimidin-4-one'>FFN</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=6gxy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gxy OCA], [https://pdbe.org/6gxy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gxy RCSB], [https://www.ebi.ac.uk/pdbsum/6gxy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gxy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TYPX_TRYBB TYPX_TRYBB] Acts as a thiol-disulfide oxidoreductase. It is spontaneously reduced by trypanothione.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Trypanosomal and leishmanial infections claim tens of thousands of lives each year. The metabolism of these single cell eukaryotic parasites differs from the human host and their enzymes thus constitute promising drug targets. Tryparedoxin (Tpx) from Trypanosoma brucei is the essential oxidoreductase in the parasite's hydroperoxide clearance cascade. Functional in vitro and in vivo assays show that a small, selective inhibitor efficiently inhibits Tpx. By X-ray crystallography, SAXS, analytical SEC, SEC-MALS, MD simulations, ITC, and NMR spectroscopy, we show how covalent binding of this monofunctional inhibitor leads to Tpx dimerization. Intra- and intermolecular inhibitor-inhibitor, protein-protein and inhibitor-protein interactions stabilize the dimer. The behavior of this efficient antitrypanosomal molecule thus constitutes an exquisite example of chemically induced dimerization with a small, monovalent ligand that can be exploited for future drug design.

Inhibitor-induced dimerization of an essential oxidoreductase from African Trypanosomes.,Wagner A, Le TA, Brennich M, Klein P, Bader N, Diehl E, Paszek D, Weickhmann AK, Dirdjaja N, Krauth-Siegel RL, Engels B, Opatz T, Schindelin H, Hellmich UA Angew Chem Int Ed Engl. 2019 Jan 3. doi: 10.1002/anie.201810470. PMID:30605929<ref>PMID:30605929</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6gxy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma brucei brucei]]
[[Category: Bader N]]
[[Category: Hellmich U]]
[[Category: Schindelin H]]
[[Category: Wagner A]]