6L0B
Crystal structure of dihydroorotase in complex with fluorouracil from Saccharomyces cerevisiae
Summary for 6L0B
| Entry DOI | 10.2210/pdb6l0b/pdb |
| Related | 6L0A |
| Descriptor | Dihydroorotase, ZINC ION, 5-FLUOROURACIL, ... (4 entities in total) |
| Functional Keywords | dihydropyrimidinase, dihydroorotase, metalloenzyme, hydrolase |
| Biological source | Saccharomyces cerevisiae (Baker's yeast) |
| Total number of polymer chains | 4 |
| Total formula weight | 166957.00 |
| Authors | Guan, H.H.,Huang, Y.H.,Huang, C.Y.,Chen, C.J. (deposition date: 2019-09-26, release date: 2020-12-02, Last modification date: 2023-11-22) |
| Primary citation | Guan, H.H.,Huang, Y.H.,Lin, E.S.,Chen, C.J.,Huang, C.Y. Structural basis for the interaction modes of dihydroorotase with the anticancer drugs 5-fluorouracil and 5-aminouracil. Biochem.Biophys.Res.Commun., 551:33-37, 2021 Cited by PubMed Abstract: 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. PubMed: 33714757DOI: 10.1016/j.bbrc.2021.03.001 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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