Structural highlights
Function
[PYRD_ECOLI] Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.[1]
Publication Abstract from PubMed
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.
Structural insights into inhibition of the drug target dihydroorotate dehydrogenase by bacterial hydroxyalkylquinolines.,Horwitz SM, Blue TC, Ambarian JA, Hoshino S, Seyedsayamdost MR, Davis KM RSC Chem Biol. 2022 Feb 7;3(4):420-425. doi: 10.1039/d1cb00255d. eCollection 2022, Apr 6. PMID:35441142[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bjornberg O, Gruner AC, Roepstorff P, Jensen KF. The activity of Escherichia coli dihydroorotate dehydrogenase is dependent on a conserved loop identified by sequence homology, mutagenesis, and limited proteolysis. Biochemistry. 1999 Mar 9;38(10):2899-908. PMID:10074342 doi:http://dx.doi.org/10.1021/bi982352c
- ↑ Horwitz SM, Blue TC, Ambarian JA, Hoshino S, Seyedsayamdost MR, Davis KM. Structural insights into inhibition of the drug target dihydroorotate dehydrogenase by bacterial hydroxyalkylquinolines. RSC Chem Biol. 2022 Feb 7;3(4):420-425. doi: 10.1039/d1cb00255d. eCollection 2022, Apr 6. PMID:35441142 doi:http://dx.doi.org/10.1039/d1cb00255d
