Reactivity of horse liver alcohol dehydrogenase with 3-methylcyclohexanols.

Abstract:

: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.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Lee KM,Dahlhauser KF,Plapp BV

doi

10.1021/bi00409a060

subject

Has Abstract

pub_date

1988-05-03 00:00:00

pages

3528-32

issue

9

eissn

0006-2960

issn

1520-4995

journal_volume

27

pub_type

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