Designing Novel Enzymes for Homogeneous Catalysis in Organic Solvents.

Abstract

Several mutants derived from the thermostable subtilisin 8397 were produced in order to create an enzyme that is more stable toward organic solvents, or more effective for peptide coupling in aqueous solution. Mutants were created with higher stability (8397/K256Y), broader substrate specificity (83 97/M222A/Y217W), and better aminolysis:hydrolysis ratio (8397/C206Q/S221C). Engineered subtilisins were shown to be useful in the coupling of glycopeptides, and in tandem with the use of glycosyltransferases, subtilisin was shown to be useful for synthesizing homogeneous glycoproteins. X-ray crystallographic and NMR structural studies of the subtilisin active site in 50% DMF support a nearly 180 deg flip in the ring of the active site histidine, which may help explain the large changes in catalysis under these conditions.

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Document Details

Document Type
Technical Report
Publication Date
Apr 20, 1999
Accession Number
ADA362504

Entities

People

  • C. H. Wong
  • M. Schuster
  • P. Sears
  • P. Wange
  • W. Fitz

Organizations

  • Scripps Research

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Carbohydrates
  • Catalysis
  • Chemical Compounds
  • Chemical Synthesis
  • Chemistry
  • Couplings
  • Glycoconjugates
  • Glycoproteins
  • Histidine
  • Molecules
  • Organic Chemistry
  • Organic Solvents
  • Solvents
  • Substrate Specificity
  • Substrates
  • X Rays

Fields of Study

  • Chemistry

Readers

  • Electrochemical Engineering/ Fuel Cell Technologies
  • Molecular and Cellular Biochemistry