MUTAGENESIS AND LAUE STRUCTURES OF ENZYME INTERMEDIATES - ISOCITRATE DEHYDROGENASE

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