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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.

SUBMITTER: Horwitz SM

PROVIDER: S-EPMC8984913 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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

Horwitz Samantha M SM Blue Tamra C TC Ambarian Joseph A JA Hoshino Shotaro S Seyedsayamdost Mohammad R MR Davis Katherine M KM

RSC chemical biology 20220207 4

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. ...[more]

PMID: 35441142

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