Structure of the RWJ-51084–bovine pancreatic β-­trypsin complex at 1.8 Å

The three-dimensional structure of bovine pancreatic trypsin complexed with the inhibitor RWJ-51084 has been determined at 1.8 Å resolution. These crystals belong to the trigonal space group P3₁21, with unit-cell parameters a = b = 53.43, c = 107.76 Å. The refined R and R_free values are 0.175 and 0.237, respectively. The carbonyl group bonded to the benzothiazole group of the inhibitor is covalently linked to the hydroxyl O atom of Ser195, forming a tetrahedral intermediate hemiketal structure. The other carbonyl O atom of the inhibitor forms a hydrogen bond with the Gln192 side-chain amide group. The benzothiazole group is oriented with the aromatic N atom of RWJ-51084 accepting a hydrogen bond from His57 NE2. The arginine side chain of the inhibitor extends into the deep and narrow pocket of the S1 specificity site of trypsin, forming a network of hydrogen bonds.