1uk0 | pdb_00001uk0
Crystal structure of catalytic domain of human poly(ADP-ribose) polymerase with a novel inhibitor
Structural highlights
FunctionPARP1_HUMAN Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.[1] [2] [3] [4] 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 PubMedThe crystal structure of human recombinant poly(ADP-ribose) polymerase (PARP) complexed with a potent inhibitor, FR257517, was solved at 3.0 A resolution. The fluorophenyl part of the inhibitor induces an amazing conformational change in the active site of PARP by motion of the side chain of the amino acid, Arg878, which forms the bottom of the active site. Consequently, a corn-shaped hydrophobic subsite, which consists of the side chains of Leu769, Ile879, Pro881, and the methylene chain of Arg878, newly emerges from the well-known active site. Inhibitor-induced structural change of the active site of human poly(ADP-ribose) polymerase.,Kinoshita T, Nakanishi I, Warizaya M, Iwashita A, Kido Y, Hattori K, Fujii T FEBS Lett. 2004 Jan 2;556(1-3):43-6. PMID:14706823[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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