The mode of action of the Protein tyrosine phosphatase 1B inhibitor Ertiprotafib
Fig 2
Ertiprotafib binds PTP1B non-specifically and induces its aggregation.
Overlay of the 2D [1H,15N]-TROSY spectra of (a) PTP1B1-301 and (c) PTP1B1-393 in the presence of ten and fifteen, respectively, molar equivalents of Ertiprotafib showing the near-complete disappearance of the peaks from the structured regions. (b) Chemical shift (top panel) and intensity (middle panel, colored in blue) changes of Ertiprotafib binding (at a molar ratio of 10) to PTP1B residues 301–393, illustrating the non-specific interaction of C-terminal disordered region much like another allosteric inhibitor, MSI-1436. Colored lines indicate one (blue), two (green) and three (yellow) s.d. from the mean CSPs. Note the large increase in intensities of the peaks of the C-terminal disordered regions at higher molar ratios of Ertiprotafib (15 molar excess, bottom panel, colored in orange).