Mutagenesis and Laue structures of enzyme intermediates: isocitrate dehydrogenase.
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.
Bolduc
J M
JM
Fred Hutchinson Cancer Research Center, Program in Structural Biology, Seattle, WA 98104, USA.
Dyer
D H
DH
Scott
W G
WG
Singer
P
P
Sweet
R M
RM
Koshland
D E
DE
Stoddard
B L
BL
D001665:Binding Sites; D002384:Catalysis; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D007521:Isocitrate Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007523:Isocitrates / Q000378:metabolism; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D009249:NADP / Q000378:metabolism; D011487:Protein Conformation
D007523:Isocitrates; D009249:NADP; C034219:isocitric acid; D007521:Isocitrate Dehydrogenase