True interaction mode of porcine pancreatic elastase with FR136706, a potent peptidyl inhibitor

The crystal structure of porcine pancreatic elastase (PPE) complexed with a potent peptidyl inhibitor, FR136706, was solved at 2.2 Å resolution. FR136706 fits snugly into the extended active site pocket. The benzene moiety of FR136706 induced dramatic movement of the side chain moiety of Arg217 and both moieties formed a π–π interaction, which has never been found previously in structures of PPE complexed with inhibitors. This novel interaction mode may lead to design of new types of inhibitors.