Structure, Function, and Inhibition of Degenerative Enzymes

Abstract

The short-term objective of this project is to establish a database which defines the binding mode of various classes of inhibitors of the serine proteases, especially elastase. 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 1.65 resolution. It forms the basis for comparison with 12 high-resolution complexes of PPE. The homologous structure of human leucocyte elastase has been determined. These two enzyme structures form a highly interesting pair for subsequent modelling studies. The variety of binding modes prompts one to be cautious in using molecular modelling in the absence of additional (experimental) information. Keywords: Molecule molecule interactions; Ligand + receptor interactions; Drug design; X-ray crystallography; Molecular structure; Chemical bonds.

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Document Details

Document Type
Technical Report
Publication Date
Sep 02, 1988
Accession Number
ADA199852

Entities

People

  • Edgar F. Meyer Jr

Organizations

  • Texas A&M University

Tags

DTIC Thesaurus Topics

  • Biochemistry
  • Biophysics
  • Chemistry
  • Classification
  • Crystal Structure
  • Crystallography
  • Databases
  • High Resolution
  • Inhibitors
  • Leukocytes
  • Military Research
  • Molecular Biology
  • Molecules
  • Small Molecules
  • Universities
  • X Rays
  • X-Ray Crystallography

Fields of Study

  • Chemistry

Readers

  • Computational Modeling and Simulation
  • Materials Science and Engineering.
  • Molecular and Cellular Biochemistry