The WPD-loop of PTPs is conformationally flexible, and can take on a range of open and even wide-open conformational states . Molecular dynamics simulations of a range of PTP1B chimeras, in which some or all of the YopH WPD-loop was grafted onto the PTP1B scaffold, indicated that there are significant differences in the conformational dynamics of the WPD-loop both compared to either parent enzyme, and when comparing the dynamics of the individual chimeras . Further, both computational and crystallographic analysis indicated the substitutions cause a population shift towards a WPD-loop closed conformation . This is the inverse of structural characterization of YopH chimeras in which parts of the PTP1B WPD-loop was grafted onto the YopH scaffold, and where substituting amino acids from the PTP1B WPD-loop into the YopH loop triggered instead a wide-open conformation in the chimeric proteins (Chimeras 2 and 3, ). Of these chimeras, only Chimera 3 was shown to have meaningful catalytic activity, although similar to the PTP1B chimeras , the activity of this chimeric construct was impaired compared to that of either parent enzyme .