High-resolution neutron structure analyses of porcine pancreatic elastase

Tamada, Taro; Kinoshita, Takayoshi*; Kurihara, Kazuo; Tada, Toshiji*; Kuroki, Ryota

Elastase is a serine protease classified in the chymotrypsin family, and is attractive target for studies of structure based drug design (SBDD). The structural information including hydrogen positions and hydration will help us to further elucidate the catalytic mechanism of serine protease. To obtain such structural information, we performed the neutron structure analyses of porcine pancreatic elastase (PPE) with and without its inhibitor using diffraction data obtained at a BIX-3 diffractometer in the research reactor JRR-3. The PPE structure in complex with/without peptidic inhibitor, which was used to mimic the tetrahedral intermediate state, was determined to 1.65/1.90 resolution, respectively. This structural information allows us to understand the role of resting state upon the catalytic reaction. Furthermore, the structural change of the active site residues including hydration structure obtained from the comparison between structures with and without inhibitor may help designing potent inhibitors by SBDD.