Reactivity of horse liver alcohol dehydrogenase with 3-methylcyclohexanols.
The specificity of horse liver alcohol dehydrogenase for cyclohexanol and its 3-methyl derivatives was investigated by stopped-flow and initial velocity kinetic studies. The (1S,3S)-3-methylcyclohexanol was 7 times more reactive (V/Km) than cyclohexanol, whereas the (1R,3R)-3-methylcyclohexanol was at least 1000 times less reactive than its enantiomer. Computer simulation of the transient reaction of NAD+ and the cyclohexanols catalyzed by the enzyme suggests that the rate of transfer of hydrogen from the alcohol to NAD+ is increased with the 1S,3S isomer. Modeling of the three-dimensional structure of the ternary complex of the enzyme suggests that the 1S,3S isomer should only bind in a productive, reactive mode, whereas the 1R,3R isomer would bind predominantly in a nonproductive, inhibitory mode.
Lee
K M
KM
Department of Biochemistry, University of Iowa, Iowa City 52242.
Dahlhauser
K F
KF
Plapp
B V
BV
D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D003511:Cyclohexanols / Q000378:metabolism*; D006736:Horses; D007536:Isomerism; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008968:Molecular Conformation; D011485:Protein Binding; D011487:Protein Conformation; D013379:Substrate Specificity
D003511:Cyclohexanols; C056571:3-methylcyclohexanol; D000426:Alcohol Dehydrogenase