Structural highlights
Function
[PYRD_TRYCC] Catalyzes the conversion of dihydroorotate to orotate with fumarate as the electron acceptor. Molecular oxygen can replace fumarate in vitro.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Trypanosoma cruzi is the etiological agent of Chagas' disease, a pathogenesis that affects millions of people in Latin America. Here, we report the crystal structure of dihydroorotate dehydrogenase (DHODH) from T. cruzi strain Y solved at 2.2A resolution. DHODH is a flavin mononucleotide containing enzyme, which catalyses the oxidation of l-dihydroorotate to orotate, the fourth step and only redox reaction in the de novo biosynthesis of pyrimidine nucleotides. Genetic studies have shown that DHODH is essential for T. cruzi survival, validating the idea that this enzyme can be considered an attractive target for the development of antichagasic drugs. In our work, a detailed analysis of T. cruzi DHODH crystal structure has allowed us to suggest potential sites to be further exploited for the design of highly specific inhibitors through the technology of structure-based drug design.
Crystal structure of Trypanosoma cruzi dihydroorotate dehydrogenase from Y strain.,Pinheiro MP, Iulek J, Cristina Nonato M Biochem Biophys Res Commun. 2008 May 9;369(3):812-7. Epub 2008 Feb 25. PMID:18302934[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pinheiro MP, Iulek J, Cristina Nonato M. Crystal structure of Trypanosoma cruzi dihydroorotate dehydrogenase from Y strain. Biochem Biophys Res Commun. 2008 May 9;369(3):812-7. Epub 2008 Feb 25. PMID:18302934 doi:10.1016/j.bbrc.2008.02.074
