The structures of human dihydroorotate dehydrogenase with and without inhibitor reveal conformational flexibility in the inhibitor and substrate binding sites

The structures of N-terminally truncated (residues Met30-Arg396) dihydroorotate dehydrogenase (DHODH) in complex with two inhibitors as well as the first structure of the enzyme to be characterized without any bound inhibitor are described. The studies have provided new insights into the dynamic features of the DHODH reaction and have provided new approaches to the design of inhibitors against DHODH.