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

Authors
Odagaki, Y Ohmoto, K Matsuoka, S Hamanaka, N Nakai, H Toda, M Katsuya, Y
Citation
Y. Odagaki et al., The crystal structure of the complex of non-peptidic inhibitor of human neutrophil elastase ONO-6818 and porcine pancreatic elastase, BIO MED CH, 9(3), 2001, pp. 647-651
Citations number
23
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY
ISSN journal
09680896 → ACNP
Volume
9
Issue
3
Year of publication
2001
Pages
647 - 651
Database
ISI
SICI code
0968-0896(200103)9:3<647:TCSOTC>2.0.ZU;2-0
Abstract
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-oxoeth yl]-2-(5-amino-6-oxo-2-phenyl-6H-pyrimidan-1-ly)acetamide (ONO-6818, 1) com plexed to porcine pancreatic elastase (PPE) has been determined at 1.86 Ang strom resolution. Analytical results provided evidence of a 1:1 complex in which the electrophilic ketone of 1 covalently bound to O gamma of Ser195 a t the active site of PPE. The role of the unique electron-withdrawing keton e of 1 has been elucidated. (C) 2001 Elsevier Science Ltd. All rights reser ved.