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 °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. The pH-rate profile for the hydrolysis of 3′-phosphoadenosine 5′-phosphosulfate (PAPS) in aqueous solution has been measured. From these data, the catalytic power(k cat/k uncat of the sulfotransferases is estimated to be in the order of 10 10–10 12. Amines - examplified by morpholine - have been found to react spontaneously eith PAPS in water at 39°C by attack at the sulfuryl group and the (5′)phosphoryl group in a ratio of 2:3. The implications of these data upon the mechanism of the N-sulfotransferases are discussed.