Scheme 1. Kinetic Scheme for Conversion of Substrate to Product and Release, Including Equilibria of the WPD-Loop.
Prototropic equilibria of the catalytic residues have been omitted. The catalytically functional species are shown in blue. Substrate can bind and product can be released from either loop-open or -closed forms, but the chemical steps can only occur from loop-closed conformations. Any factor that alters equilibria between open and closed forms may affect the extent to which the first or second step is rate-limiting at a given pH, affecting pKa values observed in a pH-rate profile.