3jqb | pdb_00003jqb

Crystal structure of pteridine reductase 1 (PTR1) from Trypanosoma brucei in ternary complex with cofactor (NADP+) and inhibitor 2-amino-5-(2-phenylethyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (DX6)

spinqualitylabelsall models 3jqb, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3jqb is a 4 chain structure with sequence from Trypanosoma brucei. This structure supersedes the now removed PDB entry 3bmh. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: CSX, DTT, DX6, NAP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q581W1_TRYB2 Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Pteridine reductase (PTR1) is a target for drug development against Trypanosoma and Leishmania species, parasites that cause serious tropical diseases and for which therapies are inadequate. We adopted a structure-based approach to the design of novel PTR1 inhibitors based on three molecular scaffolds. A series of compounds, most newly synthesized, were identified as inhibitors with PTR1-species specific properties explained by structural differences between the T. brucei and L. major enzymes. The most potent inhibitors target T. brucei PTR1, and two compounds displayed antiparasite activity against the bloodstream form of the parasite. PTR1 contributes to antifolate drug resistance by providing a molecular bypass of dihydrofolate reductase (DHFR) inhibition. Therefore, combining PTR1 and DHFR inhibitors might improve therapeutic efficacy. We tested two new compounds with known DHFR inhibitors. A synergistic effect was observed for one particular combination highlighting the potential of such an approach for treatment of African sleeping sickness. Structure-Based Design of Pteridine Reductase Inhibitors Targeting African Sleeping Sickness and the Leishmaniases.,Tulloch LB, Martini VP, Iulek J, Huggan JK, Lee JH, Gibson CL, Smith TK, Suckling CJ, Hunter WN J Med Chem. 2009 Nov 16. PMID:19916554 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Pteridine reductase

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