STRUCTURE-ACTIVITY STUDIES OF SULFATE TRANSFER - THE HYDROLYSIS AND AMINOLYSIS OF 3'-PHOSPHOADENOSINE 5'-PHOSPHOSULFATE (PAPS)

The pH-rate profile for the hydrolysis of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) in aqueous solution has been measured. Comparison with other data suggests that hydrolysis occurs by almost complete unimolecular elimination of sulfur trioxide, with weak involvement of a molecule of water in the transition state. The catalytic power (k(cat)/k(uncat)) of the sulfotransferases is estimated to be in the order of 10(10)-10(12). Amines-exemplified by morpholine-react spontaneously with PAPS in water at 39 degrees C by attack at both sulfuryl and (5')phosphoryl groups in a ratio of 2:3. The mechanism of activation of the coenzyme, PAPS, by the sulfotransferases that catalyse N-sulfation must involve suppression of its native N-phosphorylating reactivity and specific enhancement of its N-sulfating reactivity. Studies of the aminolysis of the coenzyme in aprotic solvent-water mixtures suggest how this might be accomplished.