7ca1

Crystal structure of dihydroorotase in complex with plumbagin from Saccharomyces cerevisiae

spinqualitylabelsall models 7ca1, resolution 3.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ca1 is a 4 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.6Å Ligands: 90R, KCX, LMR, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PYRC_YEAST Publication Abstract from PubMed Dihydroorotase (DHOase) is the third enzyme in the de novo biosynthesis pathway for pyrimidine nucleotides, and an attractive target for potential anticancer chemotherapy. By screening plant extracts and performing GC-MS analysis, we identified and characterized that the potent anticancer drug plumbagin (PLU), isolated from the carnivorous plant Nepenthes miranda, was a competitive inhibitor of DHOase. We also solved the complexed crystal structure of yeast DHOase with PLU (PDB entry 7CA1), to determine the binding interactions and investigate the binding modes. Mutational and structural analyses indicated the binding of PLU to DHOase through loop-in mode, and this dynamic loop may serve as a drug target. PLU exhibited cytotoxicity on the survival, migration, and proliferation of 4T1 cells and induced apoptosis. These results provide structural insights that may facilitate the development of new inhibitors targeting DHOase, for further clinical anticancer chemotherapies. Plumbagin, a Natural Product with Potent Anticancer Activities, Binds to and Inhibits Dihydroorotase, a Key Enzyme in Pyrimidine Biosynthesis.,Guan HH, Huang YH, Lin ES, Chen CJ, Huang CY Int J Mol Sci. 2021 Jun 25;22(13). pii: ijms22136861. doi: 10.3390/ijms22136861. PMID:34202294 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dihydroorotase 3D structures

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