Structure, Function, and} nhibition of Degenerative Enzymes

FIELD GROUP SUB-GROUP-Ligand + receptor interactionsi molecular modelling, drug dgesgn, X-ray crystallography. 9 ABSTRACT (Continue on reverse it necessary anu iUerZ, t, b!ck n,-rrber-The short-term objective of this project is to establish a data base which defines the binding mode of various classes of inhibitors of the serine proteases, especially elas-tase. The long-term goal is to determine general rules of binding specificity and to apply these rules to the design of novel or improved (more specific, more potent) inhibitors. By means of high-resolution X ray crystallography, the structure of native porcine pancreatic elastase (PPE, Acta Cryst. B, in press) has been refined to 1.65A resolution. It forms the basis for comparison with 12 high-resolution complexes of PPE. The homologous structure of human leucocyte elastase (EMBO Journal, 1987) 1as been determined. These two enzyme struc-tures form a highly interesting pair for subsequent modelling studies. The variety o