4i15 | pdb_00004i15

Crystal structure of TbrPDEB1

spinqualitylabelsall models 4i15, resolution 1.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4i15 is a 2 chain structure with sequence from Trypanosoma (trypanozoon) brucei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG, ZN Gene: PDEB1 (Trypanosoma (Trypanozoon) brucei) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Trypanosoma brucei cyclic nucleotide phosphodiesterase B1 (TbrPDEB1) and TbrPDEB2 have recently been validated as new therapeutic targets for human African trypanosomiasis by both genetic and pharmacological means. In this study we report the crystal structure of the catalytic domain of the unliganded TbrPDEB1 and its use for the in silico screening for new TbrPDEB1 inhibitors with novel scaffolds. The TbrPDEB1 crystal structure shows the characteristic folds of human PDE enzymes but also contains the parasite-specific P-pocket found in the structures of Leishmania major PDEB1 and Trypanosoma cruzi PDEC. The unliganded TbrPDEB1 X-ray structure was subjected to a structure-based in silico screening approach that combines molecular docking simulations with a protein-ligand interaction fingerprint (IFP) scoring method. This approach identified six novel TbrPDEB1 inhibitors with IC50 values of 10-80 muM, which may be further optimized as potential selective TbrPDEB inhibitors. Discovery of Novel Trypanosoma brucei Phosphodiesterase B1 Inhibitors by Virtual Screening against the Unliganded TbrPDEB1 Crystal Structure.,Jansen C, Wang H, Kooistra AJ, de Graaf C, Orrling KM, Tenor H, Seebeck T, Bailey D, de Esch IJ, Ke H, Leurs R J Med Chem. 2013 Mar 1. PMID:23409953 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphodiesterase

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