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| | <StructureSection load='6bu7' size='340' side='right'caption='[[6bu7]], [[Resolution|resolution]] 2.73Å' scene=''> | | <StructureSection load='6bu7' size='340' side='right'caption='[[6bu7]], [[Resolution|resolution]] 2.73Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bu7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Tryb2 Tryb2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BU7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BU7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bu7]] 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=6BU7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BU7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RD0:1-[2-(piperidin-4-yl)ethyl]-5-{5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl}-1H-indole'>RD0</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.73Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nev|4nev]], [[6btl|6btl]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RD0:2-[1-(2-piperidin-4-ylethyl)indol-5-yl]-5-(1-pyrrolidin-1-ylcyclohexyl)-1,3-thiazole'>RD0</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tb10.406.0520 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=185431 TRYB2])</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=6bu7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bu7 OCA], [https://pdbe.org/6bu7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bu7 RCSB], [https://www.ebi.ac.uk/pdbsum/6bu7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bu7 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Trypanothione-disulfide_reductase Trypanothione-disulfide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.12 1.8.1.12] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bu7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bu7 OCA], [http://pdbe.org/6bu7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bu7 RCSB], [http://www.ebi.ac.uk/pdbsum/6bu7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bu7 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q389T8_TRYB2 Q389T8_TRYB2] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Tryb2]] | + | [[Category: Trypanosoma brucei brucei TREU927]] |
| - | [[Category: Trypanothione-disulfide reductase]] | + | [[Category: Bryson S]] |
| - | [[Category: Bryson, S]] | + | [[Category: De Gasparo R]] |
| - | [[Category: Diederich, F]] | + | [[Category: Diederich F]] |
| - | [[Category: Gasparo, R De]]
| + | [[Category: Krauth-Siegel RL]] |
| - | [[Category: Krauth-Siegel, R L]] | + | [[Category: Pai EF]] |
| - | [[Category: Pai, E F]] | + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Oxidoreductase-inhibitor complex]]
| + | |
| - | [[Category: Sleeping sickness]]
| + | |
| - | [[Category: Trypanosoma]]
| + | |
| Structural highlights
6bu7 is a 2 chain structure with sequence from Trypanosoma brucei brucei TREU927. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.73Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
Q389T8_TRYB2
Publication Abstract from PubMed
The tropical diseases human African trypanosomiasis, Chagas disease, and the various forms of leishmaniasis are caused by parasites of the family of trypanosomatids. These protozoa possess a unique redox metabolism based on trypanothione and trypanothione reductase (TR), making TR a promising drug target. We report the optimization of properties and potency of cyclohexylpyrrolidine inhibitors of TR by structure-based design. The best inhibitors were freely soluble and showed competitive inhibition constants (Ki ) against Trypanosoma (T.) brucei TR and T. cruzi TR and in vitro activities (half-maximal inhibitory concentration, IC50 ) against these parasites in the low micromolar range, with high selectivity against human glutathione reductase. X-ray co-crystal structures confirmed the binding of the ligands to the hydrophobic wall of the "mepacrine binding site" with the new, solubility-providing vectors oriented toward the surface of the large active site.
Biological Evaluation and X-ray Co-crystal Structures of Cyclohexylpyrrolidine Ligands for Trypanothione Reductase, an Enzyme from the Redox Metabolism of Trypanosoma.,De Gasparo R, Brodbeck-Persch E, Bryson S, Hentzen NB, Kaiser M, Pai EF, Krauth-Siegel RL, Diederich F ChemMedChem. 2018 May 8;13(9):957-967. doi: 10.1002/cmdc.201800067. Epub 2018 Apr, 6. PMID:29624890[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ De Gasparo R, Brodbeck-Persch E, Bryson S, Hentzen NB, Kaiser M, Pai EF, Krauth-Siegel RL, Diederich F. Biological Evaluation and X-ray Co-crystal Structures of Cyclohexylpyrrolidine Ligands for Trypanothione Reductase, an Enzyme from the Redox Metabolism of Trypanosoma. ChemMedChem. 2018 May 8;13(9):957-967. doi: 10.1002/cmdc.201800067. Epub 2018 Apr, 6. PMID:29624890 doi:http://dx.doi.org/10.1002/cmdc.201800067
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