5v7t

crystal structure of PARP14 bound to N-{4-[4-(diphenylmethoxy)piperidin-1-yl]butyl}[1,2,4]triazolo[4,3-b]pyridazin-6-amine inhibitor

spinqualitylabelsall models 5v7t, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5v7t is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: 91V Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PAR14_HUMAN Enhances STAT6-dependent transcription (By similarity). Has ADP-ribosyltransferase activity. Publication Abstract from PubMed Poly(ADP-ribose) polymerases (PARPs) use nicotinamide adenine dinucleotide (NAD+) as a co-substrate to transfer ADP-ribose when it releases nicotinamide as the metabolized product. Enzymes of the PARP family play key roles in detecting and repairing DNA, modifying chromatin, regulating transcription, controlling energy metabolism, and inducing cell death. PARP14, the original member of the PARP family, has been reported to be associated with the development of inflammatory diseases and various cancer types, making it a potential therapeutic target. In this study, we purified the macrodomain-containing PARP14 enzyme and established an assay for detecting the auto-ribosylation activity of PARP14 using RapidFire high-throughput mass spectrometry and immunoradiometric assay using [3H]NAD+. Subsequently, we performed high-throughput screening using the assays and identified small-molecule hit compounds, which showed NAD+-competitive and PARP14-selective inhibitory activities. Co-crystal structures of PARP14 with certain hit compounds revealed that the inhibitors bind to the NAD+-binding site. Finally, we confirmed that the hit compounds interacted with intracellular PARP14 by a cell-based protein stabilization assay. Thus, we successfully identified primary candidate compounds for further investigation. Identification of PARP14 inhibitors using novel methods for detecting auto-ribosylation.,Yoneyama-Hirozane M, Matsumoto SI, Toyoda Y, Saikatendu KS, Zama Y, Yonemori K, Oonishi M, Ishii T, Kawamoto T Biochem Biophys Res Commun. 2017 May 6;486(3):626-631. doi:, 10.1016/j.bbrc.2017.03.052. Epub 2017 Mar 14. PMID:28315326 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Poly(ADP-ribose) polymerase 3D structures

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