Crystal Structure of the Catalytic Domain of Human PARP2 in Complex with PARP Inhibitor ABT-888

被引：70

作者：

Karlberg, Tobias ^{[1
]}

Hammarstrom, Martin ^{[1
]}

Schutz, Patrick ^{[1
]}

Svensson, Linda ^{[1
]}

Schuler, Herwig ^{[1
]}

机构：

[1] Karolinska Inst, Dept Med Biochem & Biophys, Struct Genom Consortium, S-17177 Stockholm, Sweden

来源：

BIOCHEMISTRY | 2010年 / 49卷 / 06期

基金：

加拿大健康研究院; 英国惠康基金;

关键词：

POLY(ADP-RIBOSE) POLYMERASE INHIBITOR; CLINICAL-TRIAL; DNA-REPAIR; FRAGMENT; CANCER; FAMILY; TUMORS;

D O I：

10.1021/bi902079y

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1056 / 1058

页数：3

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