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 2.2A 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 pi-pi 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.
Kinoshita
Takayoshi
T
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., 5-2-3, Tokodai, Tsukuba, Ibaraki 300-2698, Japan. takayoshi_kinoshita@po.fujisawa.co.jp
Nakanishi
Isao
I
Sato
Akihiro
A
Tada
Toshiji
T
D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004583:Electrons; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011485:Protein Binding; D011758:Pyrroles / Q000737:chemistry; D015842:Serine Proteinase Inhibitors / Q000737:chemistry*; D013552:Swine
C474655:FR136706; D011758:Pyrroles; D015842:Serine Proteinase Inhibitors; D010196:Pancreatic Elastase