View source for 7npx


==Thioredoxin glutathione reductase from Schistosoma mansoni in complex with 3-(3-Methoxyquinoxalin-2-yl)propanoic acid at 24 hours of soaking==
<StructureSection load='7npx' size='340' side='right'caption='[[7npx]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7npx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_mansoni Schistosoma mansoni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NPX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NPX 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]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EY7:3-(3-methoxyquinoxalin-2-yl)propanoic+acid'>EY7</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=7npx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7npx OCA], [https://pdbe.org/7npx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7npx RCSB], [https://www.ebi.ac.uk/pdbsum/7npx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7npx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A3Q0KFL1_SCHMA A0A3Q0KFL1_SCHMA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Fragment screening is a powerful drug discovery approach particularly useful for enzymes difficult to inhibit selectively, such as the thiol/selenol-dependent thioredoxin reductases (TrxRs), which are essential and druggable in several infectious diseases. Several known inhibitors are reactive electrophiles targeting the selenocysteine-containing C-terminus and thus often suffering from off-target reactivity in vivo. The lack of structural information on the interaction modalities of the C-terminus-targeting inhibitors, due to the high mobility of this domain and the lack of alternative druggable sites, prevents the development of selective inhibitors for TrxRs. In this work, fragments selected from actives identified in a large screen carried out against Thioredoxin Glutathione Reductase from Schistosoma mansoni (SmTGR) were probed by X-ray crystallography. SmTGR is one of the most promising drug targets for schistosomiasis, a devastating, neglected disease. Utilizing a multicrystal method to analyze electron density maps, structural analysis, and functional studies, three binding sites were characterized in SmTGR: two sites are close to or partially superposable with the NADPH binding site, while the third one is found between two symmetry related SmTGR subunits of the crystal lattice. Surprisingly, one compound bound to this latter site stabilizes, through allosteric effects mediated by the so-called guiding bar residues, the crucial redox active C-terminus of SmTGR, making it finally visible at high resolution. These results further promote fragments as small molecule probes for investigating functional aspects of the target protein, exemplified by the allosteric effect on the C-terminus, and providing fundamental chemical information exploitable in drug discovery.

Probing the Surface of a Parasite Drug Target Thioredoxin Glutathione Reductase Using Small Molecule Fragments.,Fata F, Silvestri I, Ardini M, Ippoliti R, Di Leandro L, Demitri N, Polentarutti M, Di Matteo A, Lyu H, Thatcher GRJ, Petukhov PA, Williams DL, Angelucci F ACS Infect Dis. 2021 May 5. doi: 10.1021/acsinfecdis.0c00909. PMID:33950676<ref>PMID:33950676</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7npx" style="background-color:#fffaf0;"></div>

==See Also==
*[[Thioredoxin Glutathione Reductase|Thioredoxin Glutathione Reductase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Schistosoma mansoni]]
[[Category: Angelucci F]]
[[Category: Fata F]]
[[Category: Silvestri I]]
[[Category: Williams DL]]