Specificity of alcohol dehydrogenases for sulfoxides

Sulfoxides inhibit horse liver alcohol dehydrogenase (EqADH) by binding to the enzyme-NADH complex. X-ray crystallography suggests that sulfoxides make a cation-pi interaction with the benzene ring of Phe-93 [Cho et al. (1997) Biochemistry 36, 382-389]. Structure-function relationships were examined with seven different sulfoxides binding to five human enzymes (alpha, beta1, gamma2, pi, and sigma) and three mutated forms of the horse enzyme. The human gamma2 enzyme, EqADH, and EqADH with Phe-93 replaced with Trp were selectively and strongly inhibited (Ki