There has been a recent explosion of interest in the role of loop dynamics in enzyme evolution, and the successful application of loop manipulation to protein engineering . Furthermore, the use of chimeric proteins with grafted loops is a powerful tool both for gaining biochemical insight into specific enzyme systems and as an engineering tool . In this context, loop-grafted chimeras of both PTP1B and YopH , in which some or all of the WPD-loop of one enzyme is grafted onto the other enzyme's scaffold, show intriguing structural and biochemical properties. In the parent enzymes, the WPD-loop of PTP1B is more rigid than that of YopH, which has a highly conformationally flexible WPD-loop and is also the most catalytic efficient PTP characterized to date .