5N29
An improved model of the Trypanosoma brucei CTP synthase glutaminase domain:acivicin complex.
Summary for 5N29
| Entry DOI | 10.2210/pdb5n29/pdb |
| Descriptor | CTP synthase, CHLORIDE ION (3 entities in total) |
| Functional Keywords | ctp synthase, ligase |
| Biological source | Trypanosoma brucei gambiense (strain MHOM/CI/86/DAL972) |
| Total number of polymer chains | 1 |
| Total formula weight | 30868.52 |
| Authors | de Souza, J.,Dawson, A.,Hunter, W. (deposition date: 2017-02-07, release date: 2017-04-05, Last modification date: 2025-04-09) |
| Primary citation | Oliveira de Souza, J.,Dawson, A.,Hunter, W.N. An Improved Model of the Trypanosoma brucei CTP Synthetase Glutaminase Domain-Acivicin Complex. ChemMedChem, 12:577-579, 2017 Cited by PubMed Abstract: The natural product acivicin inhibits the glutaminase activity of cytidine triphosphate (CTP) synthetase and is a potent lead compound for drug discovery in the area of neglected tropical diseases, specifically trypanosomaisis. A 2.1-Å-resolution crystal structure of the acivicin adduct with the glutaminase domain from Trypanosoma brucei CTP synthetase has been deposited in the RCSB Protein Data Bank (PDB) and provides a template for structure-based approaches to design new inhibitors. However, our assessment of that data identified deficiencies in the model. We now report an improved and corrected inhibitor structure with changes to the chirality at one position, the orientation and covalent structure of the isoxazoline moiety, and the location of a chloride ion in an oxyanion binding site that is exploited during catalysis. The model is now in agreement with established chemical principles and allows an accurate description of molecular recognition of the ligand and the mode of binding in a potentially valuable drug target. PubMed: 28333400DOI: 10.1002/cmdc.201700118 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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