Curiously, despite sharing common conserved core structures, nearly identical active sites, and common catalytic mechanisms with similar transition states, the turnover numbers among PTPs vary by several orders of magnitude . This strongly suggests an important role for loop dynamics in regulating PTP activity, a hypothesis supported by NMR and by computational studies of the human protein tyrosine phosphatase 1B (PTP1B), as well as the Yersinia virulence factor YopH ("Yersinia outer protein H"), two of the most studied PTPs to date (e.g. 3 2002; , among many others). Further experimental and computational work has suggested that loop sequence significantly impacts the conformational dynamics of the loop, which can, in turn, affect both the activity and the pHdependency of catalysis . sequence alignments and corresponding turnover numbers of wild-type YopH, and YopH Chimeras 3 and 2, and wildtype PTP1B (from which the substitutions in the chimeras were obtained). Mutated chimera residues are shown in bold. Turnover numbers were measured at pH 5.5 and 25 °C using the substrate pNPP .