3tq0 | pdb_00003tq0

Crystal structure of Leishmania major dihydroorotate dehydrogenase in complex with fumarate

spinqualitylabelsall models 3tq0, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3tq0 is a 2 chain structure with sequence from Leishmania major strain Friedlin. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: FMN, FUM, GOL, NI, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q4QEW7_LEIMA Publication Abstract from PubMed Dihydroorotate dehydrogenase (DHODH) is the fourth enzyme in the de novo pyrimidine biosynthetic pathway and has been exploited as the target for therapy against proliferative and parasitic diseases. In this study, we report the crystal structures of DHODH from Leishmania major, the species of Leishmania associated with zoonotic cutaneous leishmaniasis, in its apo form and in complex with orotate and fumarate molecules. Both orotate and fumarate were found to bind to the same active site and exploit similar interactions, consistent with a ping-pong mechanism described for class 1A DHODHs. Analysis of LmDHODH structures reveals that rearrangements in the conformation of the catalytic loop have direct influence on the dimeric interface. This is the first structural evidence of a relationship between the dimeric form and the catalytic mechanism. According to our analysis, the high sequence and structural similarity observed among trypanosomatid DHODH suggest that a single strategy of structure-based inhibitor design can be used to validate DHODH as a druggable target against multiple neglected tropical diseases such as Leishmaniasis, Sleeping sickness and Chagas' diseases. Crystal structure of dihydroorotate dehydrogenase from Leishmania major.,Cordeiro AT, Feliciano PR, Pinheiro MP, Nonato MC Biochimie. 2012 Apr 21. PMID:22542640 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dihydroorotate dehydrogenase 3D structures

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