Inhibitor‐induced structural change of the active site of human poly(ADP‐ribose) polymerase

FEBS Letters

Nakanishi, Isao²  Warizaya, Masaichi²  Kinoshita, Takayoshi²  Hattori, Kouji¹  Iwashita, Akinori³  Fujii, Takashi²  Kido, Yoshiyuki¹ 

[1] Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Kashima 2-1-6, Yodogawa-ku, Osaka 532-8514, Japan;Exploratory Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., 5-2-3, Tokodai, Tsukuba, Ibaraki 300-2698, Japan;Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Kashima 2-1-6, Yodogawa-ku, Osaka 532-8514, Japan

关键词: Poly(ADP-ribose) polymerase;    Inhibitor induced;    Crystal structure;    Synchrotron radiation;    Molecular–molecular interaction;    Structural change;    PARP;    poly(ADP-ribose) polymerase;    catPARP;    C-terminal catalytic domain of poly(ADP-ribose) polymerase;    NAD+;    nicotinamide adenine dinucleotide;    RMSD;    root mean square deviation;   

DOI  :  10.1016/S0014-5793(03)01362-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The crystal structure of human recombinant poly(ADP-ribose) polymerase (PARP) complexed with a potent inhibitor, FR257517, was solved at 3.0 Å 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.

【 授权许可】

Unknown