Crystallographic Structure of Human Dihydroorotate Dehydrogenase in Complex with the Natural Product Inhibitor Lapachol.

ABSTRACT: Dihydroorotate dehydrogenase (DHODH) is a key enzyme in the pyrimidine biosynthesis pathway, playing a critical role in cellular processes and offering therapeutic potential for antiviral, antineoplastic, and autoimmune treatments. Human DHODH (HsDHODH) utilizes ubiquinone as a second substrate, positioning its quinone-binding site as a promising target for inhibitor development. Lapachol, a natural naphthoquinone, has gained prominence as a valuable natural product for the discovery of novel therapeutic agents, thanks to its wide range of biological activities. In this study, we present the first crystal structure of HsDHODH in complex with lapachol, providing valuable insights into the interactions between this natural product and the enzyme. The structure reveals key bindi

SUBMITTER: Purificacao AD 

PROVIDER: S-EPMC12268739 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature