7nvp
From Proteopedia
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==Trypanothione reductase from Trypanosoma brucei in complex with N-{4-methoxy-3-[(4-methoxyphenyl)sulfamoyl]phenyl}-5-nitrothiophene-2-carboxamide== | ==Trypanothione reductase from Trypanosoma brucei in complex with N-{4-methoxy-3-[(4-methoxyphenyl)sulfamoyl]phenyl}-5-nitrothiophene-2-carboxamide== | ||
| - | <StructureSection load='7nvp' size='340' side='right'caption='[[7nvp]]' scene=''> | + | <StructureSection load='7nvp' size='340' side='right'caption='[[7nvp]], [[Resolution|resolution]] 2.15Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NVP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NVP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7nvp]] 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=7NVP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NVP FirstGlance]. <br> |
| - | </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=7nvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nvp OCA], [https://pdbe.org/7nvp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nvp RCSB], [https://www.ebi.ac.uk/pdbsum/7nvp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nvp ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UT2:N-{4-methoxy-3-[(4-methoxyphenyl)sulfamoyl]phenyl}-5-nitrothiophene-2-carboxamide'>UT2</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=7nvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nvp OCA], [https://pdbe.org/7nvp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nvp RCSB], [https://www.ebi.ac.uk/pdbsum/7nvp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nvp ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/Q389T8_TRYB2 Q389T8_TRYB2] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Leishmania spp. are responsible for up to 1 million new cases each year. The current therapeutic arsenal against Leishmania is largely inadequate, and there is an urgent need for better drugs. Trypanothione reductase (TR) represents a druggable target since it is essential for the parasite and not shared by the human host. Here, we report the optimization of a novel class of potent and selective LiTR inhibitors realized through a concerted effort involving X-ray crystallography, synthesis, structure-activity relationship (SAR) investigation, molecular modeling, and in vitro phenotypic assays. 5-Nitrothiophene-2-carboxamides 3, 6e, and 8 were among the most potent and selective TR inhibitors identified in this study. 6e and 8 displayed leishmanicidal activity in the low micromolar range coupled to SI > 50. Our studies could pave the way for the use of TR inhibitors not only against leishmaniasis but also against other trypanosomatidae due to the structural similarity of TR enzymes. | ||
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| + | Optimization of Potent and Specific Trypanothione Reductase Inhibitors: A Structure-Based Drug Discovery Approach.,Battista T, Federico S, Brogi S, Pozzetti L, Khan T, Butini S, Ramunno A, Fiorentino E, Orsini S, Di Muccio T, Fiorillo A, Exertier C, Di Risola D, Colotti G, Gemma S, Ilari A, Campiani G ACS Infect Dis. 2022 Aug 12;8(8):1687-1699. doi: 10.1021/acsinfecdis.2c00325., Epub 2022 Jul 26. PMID:35880849<ref>PMID:35880849</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7nvp" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Trypanosoma brucei brucei TREU927]] | ||
[[Category: Battista T]] | [[Category: Battista T]] | ||
[[Category: Colotti G]] | [[Category: Colotti G]] | ||
[[Category: Fiorillo A]] | [[Category: Fiorillo A]] | ||
[[Category: Ilari A]] | [[Category: Ilari A]] | ||
Revision as of 06:23, 26 October 2022
Trypanothione reductase from Trypanosoma brucei in complex with N-{4-methoxy-3-[(4-methoxyphenyl)sulfamoyl]phenyl}-5-nitrothiophene-2-carboxamide
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