3E0Q
Crystal structure of Schistosoma mansoni purine nucleoside phosphorylase complexed with a novel monocyclic inhibitor
Summary for 3E0Q
| Entry DOI | 10.2210/pdb3e0q/pdb |
| Related | 1TCU 1TCV 1TD1 |
| Descriptor | Purine-nucleoside phosphorylase, DIMETHYL SULFOXIDE, 6-amino-5-bromo-1,2,3,4-tetrahydropyrimidine-2,4-dione, ... (4 entities in total) |
| Functional Keywords | monocyclic inhibitor, glycosyltransferase, transferase |
| Biological source | Schistosoma mansoni (Blood fluke) |
| Total number of polymer chains | 3 |
| Total formula weight | 94522.29 |
| Authors | Pereira, H.M.,Berdini, V.,Ferri, M.R.,Cleasby, A.,Garratt, R.C. (deposition date: 2008-07-31, release date: 2009-08-18, Last modification date: 2023-08-30) |
| Primary citation | Pereira, H.M.,Berdini, V.,Ferri, M.R.,Cleasby, A.,Garratt, R.C. Crystal structure of Schistosoma purine nucleoside phosphorylase complexed with a novel monocyclic inhibitor. Acta Trop., 114:97-102, 2010 Cited by PubMed Abstract: A novel inhibitor of Schistosoma PNP was identified using an "in silico" approach allied to enzyme inhibition assays. The compound has a monocyclic structure which has not been previously described for PNP inhibitors. The crystallographic structure of the complex was determined and used to elucidate the binding mode within the active site. Furthermore, the predicted pose was very similar to that determined crystallographically, validating the methodology. The compound Sm_VS1, despite its low molecular weight, possesses an IC(50) of 1.3 microM, surprisingly low when compared with purine analogues. This is presumably due to the formation of eight hydrogen bonds with key residues in the active site E203, N245 and T244. The results of this study highlight the importance of the use of multiple conformations for the target during virtual screening. Indeed the Sm_VS1 compound was only identified after flipping the N245 side chain. It is expected that the structure will be of use in the development of new highly active non-purine based compounds against the Schistosoma enzyme. PubMed: 20122887DOI: 10.1016/j.actatropica.2010.01.010 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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