4CJX
The crystal structure of Trypanosoma brucei N5, N10- methylenetetrahydrofolate dehydrogenase-cyclohydrolase (FolD) complexed with NADP cofactor and inhibitor
Summary for 4CJX
| Entry DOI | 10.2210/pdb4cjx/pdb |
| Descriptor | C-1-TETRAHYDROFOLATE SYNTHASE, CYTOPLASMIC, PUTATIVE, GLYCEROL, DI(HYDROXYETHYL)ETHER, ... (6 entities in total) |
| Functional Keywords | oxidoreductase |
| Biological source | TRYPANOSOMA BRUCEI BRUCEI STRAIN 927/4 GUTAT10.1 |
| Total number of polymer chains | 2 |
| Total formula weight | 70524.28 |
| Authors | Eadsforth, T.C.,Hunter, W.N. (deposition date: 2013-12-23, release date: 2015-02-04, Last modification date: 2023-12-20) |
| Primary citation | Eadsforth, T.C.,Pinto, A.,Luciani, R.,Tamborini, L.,Cullia, G.,De Micheli, C.,Marinelli, L.,Cosconati, S.,Novellino, E.,Lo Presti, L.,Cordeiro Da Silva, A.,Conti, P.,Hunter, W.N.,Costi, M.P. Characterization of 2,4-Diamino-6-Oxo-1,6-Dihydropyrimidin-5-Yl Ureido Based Inhibitors of Trypanosoma Brucei Fold and Testing for Antiparasitic Activity. J.Med.Chem., 58:7938-, 2015 Cited by PubMed Abstract: The bifunctional enzyme N(5),N(10)-methylenetetrahydrofolate dehydrogenase/cyclo hydrolase (FolD) is essential for growth in Trypanosomatidae. We sought to develop inhibitors of Trypanosoma brucei FolD (TbFolD) as potential antiparasitic agents. Compound 2 was synthesized, and the molecular structure was unequivocally assigned through X-ray crystallography of the intermediate compound 3. Compound 2 showed an IC50 of 2.2 μM, against TbFolD and displayed antiparasitic activity against T. brucei (IC50 49 μM). Using compound 2, we were able to obtain the first X-ray structure of TbFolD in the presence of NADP(+) and the inhibitor, which then guided the rational design of a new series of potent TbFolD inhibitors. PubMed: 26322631DOI: 10.1021/ACS.JMEDCHEM.5B00687 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.05 Å) |
Structure validation
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