Figure 1.

(A) Aligned crystal structures of the closed WPD-loop conformations of PTP1B (light gray, WPD-loop colored blue) and YopH (dark gray, WPD-loop colored cyan), with the phosphate binding site and key catalytic loops highlighted as annotated in Panel B. A sequence alignment of the WPD-loops of PTP1B and YopH is provided above the image, with the cartoon above the sequences used to indicate the secondary structure of each residue. (B) Close-up on the active site of PTP1B showing an overlay of the closed and open WPD-loop structures, with the model substrate p-nitrophenyl phosphate (pNPP) used in this study depicted in yellow (YopH structures not shown for clarity). (C) Generalized two-step reaction mechanism ascribed to PTPs, using the same coloring as in panel B to indicate the structural location of key residues. Structures of PTP1B (in both closed and open conformations) and YopH (closed conformation only) were taken from PDB IDs 6B90(6) and 2I42,⁷ respectively.