The presence of a key catalytic residue on the WPD-loops of classic PTPs provides a direct link between loop motion and chemistry, and previous results have shown a correlation between WPD-loop dynamics and catalysis in YopH and PTP1B. Enzymes in the PTP family have variable residues within this mobile loop except for the WPD-residues themselves (Figure ). A suggestive hypothesis is that the identity of the intervening residues affects loop dynamics, and thus the catalytic rate, by altering hydrogen bonding interactions. Changes in populations of catalytically functional and nonfunctional states can also alter pH-rate dependencies, protonic equilibria, and the relative contribution of individual steps to the rate across the pH range. One goal of this study was to ascertain whether a WPD loop can be transposed intact into a related PTP and bring with it the rate and pH dependency of its source. If so, exchanging the YopH WPD-loop into PTP1B should confer a faster rate and altered pH dependency. Or, if interactions with neighboring regions of the protein are important, such a chimera might differ from either parent. In this study, the initial Chimera 0 with the YopH WPD-loop residues transposed into PTP1B was systematically restored to the native PTP1B.