3EPW
Crystal structure of Trypanosoma vivax nucleoside hydrolase in complex with the inhibitor (2R,3R,4S)-1-[(4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-2-(hydroxymethyl)pyrrolidin-3,4-diol
Summary for 3EPW
| Entry DOI | 10.2210/pdb3epw/pdb |
| Related | 1HOZ 1HP0 1KIC 2FF2 3B9G 3EPX |
| Descriptor | IAG-nucleoside hydrolase, CALCIUM ION, 7-(((2R,3R,4S)-3,4-dihydroxy-2-(hydroxymethyl)pyrrolidin-1-yl)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one, ... (5 entities in total) |
| Functional Keywords | rossmann fold, active site loops, aromatic stacking, hydrolase |
| Biological source | Trypanosoma vivax |
| Total number of polymer chains | 2 |
| Total formula weight | 75933.06 |
| Authors | Versees, W.,Goeminne, A.,Berg, M.,Vandemeulebroucke, A.,Haemers, A.,Augustyns, K.,Steyaert, J. (deposition date: 2008-09-30, release date: 2009-03-24, Last modification date: 2023-09-06) |
| Primary citation | Versees, W.,Goeminne, A.,Berg, M.,Vandemeulebroucke, A.,Haemers, A.,Augustyns, K.,Steyaert, J. Crystal structures of T. vivax nucleoside hydrolase in complex with new potent and specific inhibitors. Biochim.Biophys.Acta, 1794:953-960, 2009 Cited by PubMed Abstract: Diseases caused by parasitic protozoa remain a major health problem, mainly due to old toxic drugs and rising drug resistance. Nucleoside hydrolases are key enzymes of the purine salvage pathway of parasites from the Trypanosomatidae family and are considered as possible drug targets. N-Arylmethyl substituted iminoribitols have been developed as selective nanomolar affinity inhibitors against the purine-specific nucleoside hydrolase of Trypanosoma vivax. The current paper describes the crystal structures of the T. vivax nucleoside hydrolase in complex with two of these inhibitors, to 1.3 and 1.85 A resolution. These high resolution structures provide an accurate picture of the mode of binding of these inhibitors and their mechanism of transition-state mimicry, and are valuable tools to guide further inhibitor design. Comparison of the current structures with previously solved structures of the enzyme in complex with ground-state and transition-state-analogue inhibitors also allows for the elucidation of a detailed molecular mechanism of active-site loop opening/closing. These loop movements can be coupled to the complex kinetic mechanism of the T. vivax nucleoside hydrolase. PubMed: 19281874DOI: 10.1016/j.bbapap.2009.02.011 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.3 Å) |
Structure validation
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