Improved stability and half-life of fluorinated phosphotriesterase using Rosetta

Chembiochem. 2014 Aug 18;15(12):1761-4. doi: 10.1002/cbic.201402062. Epub 2014 Jul 25.

Abstract

Recently we demonstrated that incorporating p-fluorophenylalanine (pFF) into phosphotriesterase dramatically improved folding, thereby leading to enhanced stability and function at elevated temperatures. To further improve the stability of the fluorinated enzyme, Rosetta was used to identify multiple potential stabilizing mutations. One such variant, pFF-F104A, exhibited enhanced activity at elevated temperature and maintained activity over many days in solution at room temperature.

Keywords: amino acids; biosynthesis; computational design; half-life; noncanonical amino acids; stability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acids / chemistry
  • Amino Acids / metabolism
  • Enzyme Stability
  • Half-Life
  • Halogenation
  • Models, Molecular
  • Mutation
  • Phosphoric Triester Hydrolases / chemistry*
  • Phosphoric Triester Hydrolases / genetics
  • Phosphoric Triester Hydrolases / metabolism*
  • Temperature
  • p-Fluorophenylalanine / chemistry
  • p-Fluorophenylalanine / metabolism*

Substances

  • Amino Acids
  • p-Fluorophenylalanine
  • Phosphoric Triester Hydrolases