Phosphoryl group transfer: evolution of a catalytic scaffold.

It is proposed that enzymic phosphoryl-transfer reactions occur by concerted, step-wise, associative (phosphorane-intermediate) or dissociative (metaphosphate-intermediate) mechanisms, as dictated by the catalytic scaffold and the reactants. During the evolution of a phosphotransferase family, the mechanism of the phosphoryl-transfer reaction is in constant flux, potentially changing with each adaptation of the catalytic scaffold to a new phosphoryl-donor-acceptor pair. Phosphotransferases of the recently discovered haloacid dehalogenase superfamily of enzymes, one of the largest and most ubiquitous of the phosphotransferase families characterized to date, are described in the context of the co-evolution of the catalytic scaffold and mechanism.