The residue at this position was recently shown to affect the conformational dynamics of native PTP1B, causing a population shift towards the catalytically-active closed conformation of the WPD loop even in the ligand-free form of the enzyme. Chimera 7 (the F182Q point mutant) is about an order of magnitude slower than WT PTP1B in k cat , with no shift in the pH optimum but a broader maximum. The kinetic pKa values obtained from fits of the pH-rate data using Eq. 1 reflect the nucleophilic Cys215 (pKa1), and the general acid, Asp181 (pKa2). The kinetic pKa values for the Cys residues in both native enzymes (5.1 in PTP1B, 4.6 in YopH, Table ) are reduced from that of cysteine in solution by a hydrogen bonding network that stabilizes the thiolate anion. The kinetic pKa values of the aspartic acid in PTPs are less perturbed from the solution value. The kinetic pKa values of the chimeras differ from those of the WT parent PTP1B (Table ), particularly for the aspartic acid. Several factors can cause kinetic pKa values extracted from pH-rate data to be distorted from the true thermodynamic pKa values of ionizable catalytic residues. Because WPDloop motions correlate with catalysis in PTP1B and YopH, mutations that affect loop motion may not only affect the rates of the chemical steps, but also change the degree to which particular steps are rate-limiting within the pH range examined, leading to changes in pH-rate profiles such as those observed. The modest changes in the kinetic pKa values of the Cys residue in the Chimeras are most likely due to such effects. The greater differences in the D181 data (Table ) arise from differences in the hydrogen bonding network to D181, due to changes within the grafted loop that affect its thermodynamic pKa. The results here are consistent with the notion that differences in the loop residues and the altered hydrogen bonding patterns affect loop dynamics, and thereby alter the pH profile in ways that include broadening or moving the pH optimum. This provides an explanation for the fact that the broadness/narrowness and the optima of pH-rate profiles within the PTP family vary despite conservation of their ionizable catalytic residues.