3u9h | pdb_00003u9h

Complex structure of human tankyrase 2 with nicotinamide

spinqualitylabelsall models 3u9h, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3u9h is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, NCA, PEG, SO4, ZN Gene: TNKS2, PARP5B, TANK2, TNKL (Homo sapiens) Activity: NAD(+) ADP-ribosyltransferase, with EC number 2.4.2.30 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Tankyrases are poly(ADP-ribose) polymerases that have many cellular functions. They play pharmaceutically important roles, at least in telomere homeostasis and Wnt signaling, by covalently ADP-ribosylating target proteins and consequently regulating their functions. These features make tankyrases potential targets for treatment of cancer. We report here crystal structures of human tankyrase 2 catalytic fragment in complex with a by-product, nicotinamide and with selective inhibitors of tankyrases (IWR-1) and PARPs 1 and 2 (olaparib). Binding of these inhibitors to tankyrase 2 induce specific conformational changes. The crystal structures explain the selectivity of the inhibitors, reveal the flexibility of a substrate binding loop and explain existing structure-activity relationship data. The first crystal structure of a PARP enzyme in complex with a potent inhibitor, IWR-1, which does not bind to the widely-utilized nicotinamide-binding site makes the structure valuable also for development of PARP inhibitors in general. Structural Basis of Selective Inhibition of Human Tankyrases.,Narwal M, Venkannagari H, Lehtio L J Med Chem. 2012 Jan 10. PMID:22233320 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Poly (ADP-ribose) polymerase

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