Fig. 3: PTP1B D181A/Q262A is a product trapping mutant.
From: Structure guided studies of the interaction between PTP1B and JAK
a The structure of PTP1B 560 D181A/Q262A (green) shows that the WPD loop is closed even in the apo form, compared to the wild-type protein (white, PDB 2HNQ [28]). b Interactions between the PTP1B phosphatase domain, JAK2 activation loop peptide and free phosphate. The free phosphate is coordinated by the side chains of Cys 215, Arg 221, Gln 266 and the substrate tyrosine. The phosphate (orange/red) has shifted in comparison to the tungstate product complex (grey) (PDB 2HNQ [28]) and has displaced a water coordinated by Q266 in the wild-type structure. c Sequences of each JAK activation loop peptide used in this study. d Overlay of all four structures of PTP1B D181A/Q262A bound to the JAK1, JAK2, JAK3 or TYK2 peptide shows that the product peptide and phosphate remains trapped in the catalytic pocket in every case.
