Diffraction data for Chimeras 3 and 4 were collected on the Stanford Synchrotron Radiation Lightsource (SSRL) beamline 9-2, and diffraction data for Chimera 7 were collected on a home source (Rigaku Micromax 007/Raxis IV++) (Table ). Data were indexed and processed using DENZO and SCALEPACK in the HKL2000 program suite. Molecular replacement was performed with Phaser-MR as implemented in Phenix 57 and CCP4 55 using WT PTP1B (PDB ID 3I80 ) with active-site water molecules manually removed as a search model. Phenix.refine was used for refinement. Model building was performed using Coot. All figures of the enzyme structures and structural alignments therein were made using PyMOL (The PyMOL Molecular Graphics System, Version 1.2r3pre, Schrödinger, LLC.).