Mutagenesis and Laue structures of enzyme intermediates: isocitrate dehydrogenase

Science. 1995 Jun 2;268(5215):1312-8. doi: 10.1126/science.7761851.


Site-directed mutagenesis and Laue diffraction data to 2.5 A resolution were used to solve the structures of two sequential intermediates formed during the catalytic actions of isocitrate dehydrogenase. Both intermediates are distinct from the enzyme-substrate and enzyme-product complexes. Mutation of key catalytic residues changed the rate determining steps so that protein and substrate intermediates within the overall reaction pathway could be visualized.

Publication types

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

MeSH terms

  • Binding Sites
  • Catalysis
  • Computer Graphics
  • Crystallography, X-Ray*
  • Isocitrate Dehydrogenase / chemistry*
  • Isocitrate Dehydrogenase / genetics
  • Isocitrate Dehydrogenase / metabolism
  • Isocitrates / metabolism
  • Kinetics
  • Mutagenesis, Site-Directed*
  • NADP / metabolism
  • Protein Conformation


  • Isocitrates
  • NADP
  • isocitric acid
  • Isocitrate Dehydrogenase