Structure of the catalytic fragment of poly(ADP-ribose) polymerase from chicken

被引:218
作者
Ruf, A
DeMurcia, JM
DeMurcia, GM
Schulz, GE
机构
[1] INST ORGAN CHEM & BIOCHEM,D-79104 FREIBURG,GERMANY
[2] ECOLE SUPER BIOTECHNOL,CNRS,UPR 9003,F-67400 ILLKIRCH GRAFFENS,FRANCE
关键词
DNA repair; NAD; nicotinamide analogue; X-ray crystallography; bacterial toxins;
D O I
10.1073/pnas.93.15.7481
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The crystal structures of the catalytic fragment of chicken poly(ADP-ribose) polymerase [NAD(+) ADP-ribosyltransferase; NAD(+):poly(adenosine-diphosphate-D-ribosyl)-acceptor ADP-D-ribosyltransferase, EC 2.4.2.30] with and without a nicotinamide-analogue inhibitor have been elucidated. Because this enzyme is involved in the regulation of DNA repair, its inhibitors are of interest for cancer therapy, The inhibitor shows the nicotinamide site and also suggests the adenosine site. The enzyme is structurally related to bacterial ADP-ribosylating toxins but contains an additional alpha-helical domain that is suggested to relay the activation signal issued on binding to damaged DNA.
引用
收藏
页码:7481 / 7485
页数:5
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