Alcohol Dehydrogenase Structure-Activity Relationships

Reactivity of horse liver alcohol dehydrogenase with 3-methylcyclohexanols

“…An enhanced reactivity of 7-fold due to one methyl group is consistent with observations that one methylene unit im-proves hydrophobic binding interactions by about 2-fold (Hansch et al, 1972) and that changing a methionine to leucine in the substrate-binding pocket of yeast alcohol dehydrogenase increased reactivity 10-fold (Ganzhorn et al, 1987). In the latter case, there was a 2-fold increase in binding and a 5-fold increase in the hydrogen-transfer rate.…”

Ambivalent active-site-directed inactivators of liver alcohol dehydrogenase

“…As discussed above, 2 appeared to fit optimally into the active site. As expected for reagents that should bind into the hydrophobic active site (Brandén et al, 1975;Hansch et al, 1972), the affinities (1 /K\) and reactivities (kj/K]) of the homologous reagents 1-5 generally increased as the length of the alkyl chain increased. The data for 1 and 3-5 fit a linear free-energy relationship with a value of AG°o f 300 cal/mol per methylene unit bound in the presence or absence of NAD+.…”

“…The other reagents were tested by the standard procedure, and the apparent bimolecular rate constants are presented in Table II. Inactivation by the homologous series of reagents 1-5 in the absence of nucleotides increases as the length of the alkyl chain increases, as expected for the hydrophobic active site (Brándén et al, 1975;Hansch et al, 1972). The aryl or aralkyl reagents 6-9 inactivate even faster.…”

Roles of zinc ion and reduced coenzyme in the formation of a transient chemical intermediate during the equine liver alcohol dehydrogenase catalyzed reduction of an aromatic aldehyde

“…The conclusion that I binds to a highly polar site is consistent with the existence of the well-characterized nonpolar (hydrophobic) pocket presumed to be adjacent to the site. (This hydrophobic pocket has been proposed to be the region responsible for binding the aliphatic or aromatic moieties of substrates and/or inhibitors (Sund and Theorell, 1962; Sigman, 1967; Sarma and Woronick, 1972;Hansch et al, 1972). )…”