Histidine residues in human phenol sulfotransferases.

Sulfotransferases are phase II drug-metabolizing enzymes that catalyze the sulfation of hydroxyl-containing compounds, leading to detoxification of xenobiotic toxicants. The universal sulfuryl donor is adenosine 3'-phosphate-5'-phosphosulfate. Human simple phenol sulfotransferase (P-PST) is one of the major human sulfotransferases that catalyze the sulfation of most phenols. Human monoamine phenol sulfotransferase (M-PST) has high affinity for monoamines and also catalyzes the sulfation of simple phenols at high substrate concentrations. In this report, the amino acid modification method was used for studies of His residues in the active site of P-PST and M-PST. The His specific modification reagent diethylpyrocarbonate was used for the modification of His residues in P-PST and M-PST. Diethylpyrocarbonate inactivation kinetic data suggest that there is one His residue in the active site that is critical for catalytic activity of both P-PST and M-PST. The modification has no effect on phenol or monoamine substrate binding for M-PST, but it does have an effect on adenosine 3'-phosphate-5'-phosphosulfate binding with M-PST. The experimental results agree with amino acid sequence alignment, mutation, and the crystal structures of P-PST and M-PST and suggest that His108 is the only critical His residue in both P-PST and M-PST. The differing roles His108 plays in P-PST and M-PST may explain the substrate specificity of the two isoforms.