Binding-Pocket and Lid-Regi on Substitutions Render Human STING Sensitive to the Species-Specific Drug DMXAA Graphical

In Brief The anticancer drug DMXAA specifically activates the STING pathway in a species-dependent manner. Gao et al. combine calorimetric, structural, and cellular studies to investigate the mechanism underlying DMXAA species selectivity. They find a critical role for a lid residue at position 230 and unveil the structural basis for the mouse specificity of DMXAA. This work also suggests ways to render human STING responsive to DMXAA.