This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
3mhu is a 2 chain structure with sequence from Leishmania major. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
The enzyme dihydroorotate dehydrogenase (DHODH) has been suggested as a promising target for the design of trypanocidal agents. We report here the discovery of novel inhibitors of Trypanosoma cruzi DHODH identified by a combination of virtual screening and ITC methods. Monitoring of the enzymatic reaction in the presence of selected ligands together with structural information obtained from X-ray crystallography analysis have allowed the identification and validation of a novel site of interaction (S2 site). This has provided important structural insights for the rational design of T. cruzi and Leishmania major DHODH inhibitors. The most potent compound (1) in the investigated series inhibits TcDHODH enzyme with Kiapp value of 19.28 muM and possesses a ligand efficiency of 0.54 kcal mol(-1) per non-H atom. The compounds described in this work are promising hits for further development.
Novel insights for dihydroorotate dehydrogenase class 1A inhibitors discovery.,Cheleski J, Rocha JR, Pinheiro MP, Wiggers HJ, da Silva AB, Nonato MC, Montanari CA Eur J Med Chem. 2010 Dec;45(12):5899-909. Epub 2010 Oct 7. PMID:20965617[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
↑ Cheleski J, Rocha JR, Pinheiro MP, Wiggers HJ, da Silva AB, Nonato MC, Montanari CA. Novel insights for dihydroorotate dehydrogenase class 1A inhibitors discovery. Eur J Med Chem. 2010 Dec;45(12):5899-909. Epub 2010 Oct 7. PMID:20965617 doi:10.1016/j.ejmech.2010.09.055
