Crystal Structure of the Catalytic Domain of Human PARP2 in Complex with PARP Inhibitor ABT-888
Crystal Structure of the Catalytic Domain of Human PARP2 in Complex with PARP Inhibitor ABT-888
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DOI：
10.1021/bi902079y
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发表时间：
2010-02-16
期刊：
影响因子：
2.9
通讯作者：
Schuler, Herwig
中科院分区：
文献类型：
--
作者：
Karlberg, Tobias;Hammarstrom, Martin;Schuler, Herwig
聚adp核糖聚合酶（parp）催化adp核糖从NAD（+）转移到其底物蛋白的特定残基或生长的adp核糖链。PARP活性参与染色质重塑、转录控制和DNA修复等过程。PARP活性抑制剂可能在癌症治疗中有用。PARP2是与PARP1最相似的家族成员，两者可以作为异源二聚体共同作用。我们用x射线晶体学确定了人类PARP2催化结构域的两种结构：与PARP抑制剂3-氨基苯甲酰胺和ABT-888的配合物。这些结果有助于我们了解结构特征和化合物性质，可用于开发人类adp -核糖基转移酶的选择性抑制剂。
Poly-ADP-ribose polymerases (PARPs) catalyze transfer of ADP-ribose from NAD(+) to specific residues in their substrate proteins or to growing ADP-ribose chains. PARP activity is involved in processes Such its chromatin remodeling, transcription control, and DNA repair. Inhibitors of PARP activity may be useful in cancer therapy. PARP2 is the family member that is most similar to PARP1, and the two can act together as heterodimers. We used X-ray crystallography to determine two structures of the catalytic domain of human PARP2: the complexes with PARP inhibitors 3-aminobenzamide and ABT-888. These results contribute to our understanding of structural features and compound properties that call be employed to develop selective inhibitors of human ADP-ribosyltransferases.