7CA1

Crystal structure of dihydroorotase in complex with plumbagin from Saccharomyces cerevisiae

7CA1 の概要

• エントリーDOI: 10.2210/pdb7ca1/pdb
• 関連するPDBエントリー: 6L0A 6L0B
• 分子名称: Dihydroorotase, (2S)-2-hydroxybutanedioic acid, ZINC ION, ... (4 entities in total)
• 機能のキーワード: dihydropyrimidinase, dihydroorotase, metalloenzyme, hydrolase
• 由来する生物種: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 167081.22

構造登録者

Guan, H.H.,Huang, Y.H.,Huang, C.Y.,Chen, C.J. (登録日: 2020-06-08, 公開日: 2021-06-09, 最終更新日: 2023-11-29)

主引用文献

Guan, H.H.,Huang, Y.H.,Lin, E.S.,Chen, C.J.,Huang, C.Y.
Plumbagin, a Natural Product with Potent Anticancer Activities, Binds to and Inhibits Dihydroorotase, a Key Enzyme in Pyrimidine Biosynthesis.
Int J Mol Sci, 22:-, 2021

PubMed Abstract: 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 , 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.

PubMed: 34202294
DOI: 10.3390/ijms22136861

実験手法

X-RAY DIFFRACTION (3.6 Å)