Extended Data Fig. 2: Structural modeling of SCA1 binding to SHP1.
From: A druggable redox switch on SHP1 controls macrophage inflammation
a, Covalent docking model of SCA1 with auto-inhibited form of SHP1 (PDB ID: 2B3O) showing shallow binding surface for anchorage of SCA1. N-SH2, C-SH2 and PTP domains represented in orange, gray and blue respectively. b, (Left) Crystal structures alignment of auto-inhibited SHP2 with (green, PDB ID: 6MD9) or without allosteric inhibitor isoxazolo-pyridinone 3 (yellow, inhibitor as stick-ball mode, PDB ID: 6CMP), showing similar conformation. (Right) Crystal structures alignment of apo auto-inhibited SHP2 (yellow, PDB ID: 6CMP) and apo auto-inhibited SHP1 (cyan, PDB ID: 2B3O) showing significant difference in the C-SH2 domain orientation and lack of allosteric site in inactive SHP1. c, Covalent docking of SCA1 to inactive SHP1 (represented in orange, gray and blue) aligned with auto-inhibited SHP2 (yellow, PDB ID: 6CMP) showing a different SCA1 occupancy location. d, Structural alignment of hypothetical binding mode of SCA1 to inactive SHP1 (represented in orange, gray and blue) with crystal structure of inactive SHP2 with allosteric inhibitor isoxazolo-pyridinone 3 (green, PDB ID: 6MD9), showing incompatibility with C-SH2 of SHP2 assuming binding to hinge cysteine on SHP2. e, Sequence alignment of SHP1 (PTN6) and SHP2 (PTN11) showing SCA1 binding site residues (orange thin lines) on SHP1 and their corresponding residues on SHP2.
