title: Crystal structure of the complex of porcine pancreatic elastase with TEI-8362.
abstract: The crystal structure of porcine pancreatic elastase (PPE) complexed with a new benzoxazinone inhibitor, TEI-8362, of human neutrophil elastase (HNE) was determined at 1.8 A resolution. The hydroxyl oxygen of Ser195 opened the benzoxazinone by nucleophilic attack and formed a covalent bond with the carbonyl carbon. Hydrophobic interaction between the terminal benzene of TEI-8362 and the S4 pocket is reinforced by the side chain of Arg217 and has an impact on the ligand binding conformation. Two additional interactions with the oxyanion hole and His57 are introduced to the benzoxazinone structure of TEI-8362. These combinatorial interactions will also exist in HNE and cause high preference of TEI-8362 for HNE.
authors.affiliation: Teijin Institute for Bio-Medical Research, Asahigaoka, Hino, Tokyo 191-8512, Japan. ma.koizumi@teijin.co.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Koizumi
authors.forename: Emiko
authors.initials: E
authors.lastname: Muratani
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Fujii
authors.forename: Midori
authors.initials: M
authors.lastname: Takimoto-Kamimura
mesh_terms: D000818:Animals; D001665:Binding Sites; D002087:Butyrates / Q000737:chemistry*; D002219:Carbamates / Q000737:chemistry*; D003198:Computer Simulation; D018360:Crystallography, X-Ray / Q000379:methods*; D004791:Enzyme Inhibitors / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D046911:Macromolecular Substances; D008958:Models, Molecular; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000648:ultrastructure*; D011485:Protein Binding; D011487:Protein Conformation; D013556:Swine, Miniature
chemical_list: D002087:Butyrates; D002219:Carbamates; D004791:Enzyme Inhibitors; D046911:Macromolecular Substances; C119150:TEI 8362; D010196:Pancreatic Elastase