3mjy | pdb_00003mjy

Crystal structure of dihydroorotate dehydrogenase from Leishmania major in complex with 5-Aminoorotic acid

spinqualitylabelsall models 3mjy, resolution 1.96Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3mjy is a 2 chain structure with sequence from Leima. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FMN, GOL, IJZ, SO4 Related: 3mhu, 3gye, 3c3n Gene: LmjF16.0530 (LEIMA) Activity: Dihydroorotate oxidase (fumarate), with EC number 1.3.98.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dihydroorotate dehydrogenase

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