Mutant Proteins--Enzymes to Hydrolyze Toxic Organophosphates

Abstract

This work focuses on the creation of new catalytic activities by modification of existing enzymes. To this end, techniques for the synthesis of large genes have been developed together with a complementation system for the expression and correct folding of proteins that are normally self-processing but that have mutated so they can no longer process themselves. (Concurrent expression of the pro-sequence and the mature protein sequence encoded on separate but compatible plasmids accomplishes this purpose; the pro-sequence apparently performs the role of a chaperoning in this case). The enzymes studied are two serine hydrolases, alpha protease and B-lactamase. For a-lytic proteases the new activity sought was the ability to hydrolyze organophosphates rather than being irreversibly inhibited by these substances. For Beta lactamase we created a structural variant that had a dramatically different catalytic role on the normal beta lactam substrates.

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Document Details

Document Type
Technical Report
Publication Date
Jun 17, 1991
Accession Number
ADA238553

Entities

People

  • John H. Richards

Organizations

  • California Institute of Technology

Tags

Communities of Interest

  • Energy and Power Technologies

DTIC Thesaurus Topics

  • Acids
  • Amino Acids
  • Anti-Bacterial Agents
  • Biochemistry
  • Catalysis
  • Cell Line
  • Cellular Structures
  • Chemical Engineering
  • Chemical Synthesis
  • Chemistry
  • Crystal Structure
  • Enzymes
  • Hydrolysis
  • Molecules
  • Mutant Proteins
  • Organophosphates
  • Proteins

Readers

  • Molecular Genetics
  • Molecular and Cellular Biochemistry
  • Neurotoxicology