Fig. 2

Binding mode of epacadostat and spectral markers for O and N-based inhibitors. a Crystal structure of the hIDO1-epacadostat complex. The interactions between epacadostat and the protein matrix are indicated by the red dotted lines, while the intramolecular H-bonds within epacadostat are indicated by the blue dotted lines. The bottom inset shows the 2Fo-Fc map of the epacadostat and the heme, contoured at 1.0 σ (colored in gray). It is overlaid with the anomalous difference Fourier map contoured at 9.0 σ (shown in red), confirming the position of the Br atom. b, c Optical absorption spectra of hIDO1 in complex with epacadostat or NLG919, which coordinates to the heme iron via its oxygen or nitrogen atom, respectively, in the ferric state (black trace) and ferrous state (red trace). The right inset in b shows a schematic illustration of the epacadostat–protein interactions. It should be noted that the bound epacadostat is displayed as a protonated form, but its true protonation state requires additional studies