6l0k

Crystal structure of dihydroorotase in complex with malate at pH9 from Saccharomyces cerevisiae

spinqualitylabelsall models 6l0k, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6l0k 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 3.3Å Ligands: 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 of pyrimidine nucleotides and considered an attractive target for potential antimalarial, anticancer, and antipathogen chemotherapy. Whether the FDA-approved clinical drug 5-fluorouracil (5-FU) that is used to target the enzyme thymidylate synthase for anticancer therapy can also bind to DHOase remains unknown. Here, we report the crystal structures of DHOase from Saccharomyces cerevisiae (ScDHOase) complexed with malate, 5-FU, and 5-aminouracil (5-AU). ScDHOase shares structural similarity with Escherichia coli DHOase. We also characterized the binding of 5-FU and 5-AU to ScDHOase by using the fluorescence quenching method. These complexed structures revealed that residues Arg18, Asn43, Thr106, and Ala275 of ScDHOase were involved in the 5-FU (PDB entry 6L0B) and 5-AU binding (PDB entry 6L0F). Overall, these results provide structural insights that may facilitate the development of new inhibitors targeting DHOase and constitute the 5-FU and 5-AU interactomes for further clinical chemotherapies. Structural basis for the interaction modes of dihydroorotase with the anticancer drugs 5-fluorouracil and 5-aminouracil.,Guan HH, Huang YH, Lin ES, Chen CJ, Huang CY Biochem Biophys Res Commun. 2021 Apr 30;551:33-37. doi:, 10.1016/j.bbrc.2021.03.001. Epub 2021 Mar 11. PMID:33714757 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dihydroorotase 3D structures

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