New Insights from Crystallographic Data: Diversity of Structural Motifs and Molecular Recognition Properties between Groups of IDO1 Structures

A large amount of crystallographic structures of IDO1 in different ligand-bound and unbound states has been disclosed over the last decade. Yet, only few of these structures have been exploited for structure based drug design (SBDD) campaigns. In this study, we carried out an analysis of structural motifs and molecular recognition properties of three groups of IDO1 structures: (i) structures containing the heme group and inhibitors in the catalytic site; (ii) heme-free structures of IDO1; (iii) substrate-bound structures of IDO1. Results suggest that unrelated conformations of the enzyme have been solved with different ligand-induced changes of secondary motifs which localize even in remote regions from the catalytic site. Moreover, the study identified an uncharted region of the molecular recognition space covered by IDO1 binding sites that may guide the selection of diverse structures for additional SBDD studies aimed at the identification of novel lead compounds with differentiated chemical scaffolds.