1. X-ray diffraction analysis of the inhibition of porcine pancreatic elastase by a peptidyl trifluoromethylketone.
- Author
-
Takahashi LH, Radhakrishnan R, Rosenfield RE Jr, Meyer EF Jr, Trainor DA, and Stein M
- Subjects
- Animals, Binding Sites, Hydrogen Bonding, Swine, X-Ray Diffraction, Oligopeptides pharmacology, Pancreatic Elastase antagonists & inhibitors
- Abstract
X-ray crystallographic data to 2.57 A resolution (1 A = 0.1 nm) have been measured for the complex of a peptidyl trifluoromethylketone inhibitor with porcine pancreatic elastase (PPE); R = 0.14. The inhibitor forms a stable complex with the enzyme by means of a covalent attachment to active site Ser195O gamma, resulting in a hemiketal moiety with tetrahedral geometry. The tripeptide protion binds as an antiparallel beta-sheet, with four hydrogen bonds augmenting the active-site covalent linkage, Ki = 9.5 microM. His57 exhibits a bifurcated H-bond to both Ser195O gamma and an F atom of the inhibitor. This study is one of a series which explores the binding geometry of a variety of small substrates and inhibitors to PPE. This peptidyl-PPE complex affords insight into the binding geometry of a novel trifluoromethylketone moiety to a serine proteinase.
- Published
- 1988
- Full Text
- View/download PDF