The crystal structure of the complex of non-peptidic inhibitor of human neutrophil elastase ONO-6818 and porcine pancreatic elastase Original Research Article

The crystal structure of a new inhibitor of human neutrophil elastase (HNE), N-[2-[5-(tert-butyl)-1,3,4-oxadiazol-2-yl]-(1RS)-1-(methylethyl)-2-oxoethyl]-2-(5-amino-6-oxo-2-phenyl-6H-pyrimidin-1-ly)acetamide (ONO-6818, 1) complexed to porcine pancreatic elastase (PPE) has been determined at 1.86 Å resolution. Analytical results provided evidence of a 1:1 complex in which the electrophilic ketone of 1 covalently bound to Oγ of Ser195 at the active site of PPE. The role of the unique electron-withdrawing ketone of 1 has been elucidated.