7NVP
Trypanothione reductase from Trypanosoma brucei in complex with N-{4-methoxy-3-[(4-methoxyphenyl)sulfamoyl]phenyl}-5-nitrothiophene-2-carboxamide
This is a non-PDB format compatible entry.
Summary for 7NVP
| Entry DOI | 10.2210/pdb7nvp/pdb |
| Descriptor | N(1),N(8)-bis(glutathionyl)spermidine reductase, FLAVIN-ADENINE DINUCLEOTIDE, N-{4-methoxy-3-[(4-methoxyphenyl)sulfamoyl]phenyl}-5-nitrothiophene-2-carboxamide, ... (6 entities in total) |
| Functional Keywords | trypanothione, neglected tropical diseases, inhibition, redox equilibrium, oxidoreductase |
| Biological source | Trypanosoma brucei brucei (strain 927/4 GUTat10.1) |
| Total number of polymer chains | 2 |
| Total formula weight | 109970.28 |
| Authors | Battista, T.,Fiorillo, A.,Colotti, G.,Ilari, A. (deposition date: 2021-03-15, release date: 2022-03-30, Last modification date: 2024-10-23) |
| Primary citation | 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. Optimization of Potent and Specific Trypanothione Reductase Inhibitors: A Structure-Based Drug Discovery Approach. Acs Infect Dis., 8:1687-1699, 2022 Cited by PubMed Abstract: spp. are responsible for up to 1 million new cases each year. The current therapeutic arsenal against 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 TR inhibitors realized through a concerted effort involving X-ray crystallography, synthesis, structure-activity relationship (SAR) investigation, molecular modeling, and phenotypic assays. 5-Nitrothiophene-2-carboxamides , , and were among the most potent and selective TR inhibitors identified in this study. and 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. PubMed: 35880849DOI: 10.1021/acsinfecdis.2c00325 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.153 Å) |
Structure validation
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