This wide-open conformation is clearly catalytically inactive. However, Chimera 3, which crystallizes in this wide-open conformation in its unliganded form, shows catalytic activity comparable to an average PTP ( , kcat 5.1 s -1 ). Furthermore, similar wide-open conformations have been observed in three PTPs from different PTP subgroups: STEP, LYP, and GLEP1 , pointing to a potentially functional role for this conformation, likely in the allosteric regulation of these enzymes. The putative importance of this conformation to allosteric regulation is further supported by the fact that small molecule inhibitors have been designed that displace the WPD-loop tryptophan of PTPRZ and RPTPg , locking the WPD-loop into a similar wide-open conformation. More globally, it is intriguing that subtle perturbations to the WPD-loop sequence in both PTP1B and YopH can have such radical impact on the dynamical behavior of the loop, and thus also, in turn, the solubility and activity of the resulting constructs .