Abstract
The crystal structure of the catalytic domain 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 structural 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-shape 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. This observation should provide a new concept in PARP inhibitor design.
