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New Insights from Crystallographic Data: Diversity of Structural Motifs and Molecular Recognition Properties between Groups of IDO1 Structures
Author(s) -
Mammoli Andrea,
Coletti Alice,
Ballarotto Marco,
Riccio Alessandra,
Carotti Andrea,
Grohmann Ursula,
Camaioni Emidio,
Macchiarulo Antonio
Publication year - 2020
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000116
Subject(s) - structural motif , ligand (biochemistry) , chemistry , substrate (aquarium) , molecular recognition , functional diversity , active site , stereochemistry , binding site , catalysis , computational biology , crystallography , combinatorial chemistry , molecule , receptor , biology , biochemistry , organic chemistry , ecology
A large number of crystallographic structures of IDO1 in different ligand‐bound and ‐unbound states have been disclosed over the last decade. Yet, only a few of them have been exploited for structure‐based drug design (SBDD) campaigns. In this study, we analyzed the structural motifs and molecular‐recognition properties of three groups of IDO1 structures: 1) structures containing the heme group and inhibitors in the catalytic site; 2) heme‐free structures of IDO1; 3) substrate‐bound structures of IDO1. The results suggest that unrelated conformations of the enzyme have been solved with different ligand‐induced changes of secondary motifs that localize even in regions remote from the catalytic site. Moreover, the study identified an uncharted region of molecular‐recognition space covered by IDO1 binding sites that could guide the selection of diverse structures for additional SBDD studies aimed at the identification of novel lead compounds with differentiated chemical scaffolds.