Structural insights into inhibition of the drug target dihydroorotate dehydrogenase by bacterial hydroxyalkylquinolines

Abstract

Hydroxyalkylquinolines (HAQs) are ubiquitious natural products but their interactions with associated protein targets remain elusive. We report X-ray crystal structures of two HAQs in complex with dihydroorotate dehydrogenase (DHODH). Our results reveal the structural basis of DHODH inhibition by HAQs and open the door to downstream structure–activity relationship studies.