Redesign of the coenzyme specificity of a dehydrogenase by protein engineering

Nature. 1990 Jan 4;343(6253):38-43. doi: 10.1038/343038a0.


Directed mutagenesis and molecular modelling have been used to identify a set of amino-acid side chains in glutathione reductase that confer specificity for the coenzyme NADP+. Systematic replacement of these amino acids, all of which occur in a 'fingerprint' structural motif in the NADP+-binding domain, leaves the substrate specificity unchanged but converts the enzyme into one displaying a marked preference for the coenzyme NAD+.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Computer Graphics
  • DNA Mutational Analysis
  • Glutathione Reductase / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • NAD / metabolism*
  • NADP / metabolism*
  • Protein Engineering*
  • Structure-Activity Relationship
  • Substrate Specificity


  • NAD
  • NADP
  • Glutathione Reductase