ArticleBiomolecules2023
Complexed Crystal Structure of the Dihydroorotase Domain of Human CAD Protein with the Anticancer Drug 5-Fluorouracil.
Article in Biomolecules, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Crystal structure of Methanococcus jannaschii dihydroorotase with substrate bound.Acta crystallographica. Section F, Structural biology communications · 2026Article
- Conformational Dynamics of the Active Site Loop in Dihydroorotase Highlighting the Limitations of Loop-In Structures for Inhibitor Docking.International journal of molecular sciences · 2025Article
- Bioactive Potential ofPlants (Basel, Switzerland) · 2025Article
- The Loop-In Binding Mode of Dihydroorotase: Implications for Ligand Binding and Therapeutic Targeting.International journal of molecular sciences · 2025Review
- Inhibition of SARS-CoV-2 Nsp9 ssDNA-Binding Activity and Cytotoxic Effects on H838, H1975, and A549 Human Non-Small Cell Lung Cancer Cells: Exploring the Potential ofInternational journal of molecular sciences · 2024Article
- Binding Pattern and Structural Interactome of the Anticancer Drug 5-Fluorouracil: A Critical Review.International journal of molecular sciences · 2024Review
- Cytotoxicity and Multi-Enzyme Inhibition ofPlants (Basel, Switzerland) · 2024Article
- Crystal Structure of DNA Replication Protein SsbA Complexed with the Anticancer Drug 5-Fluorouracil.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Dihydroorotase (DHOase) is the third enzyme in the pathway used for the biosynthesis of pyrimidine nucleotides. In mammals, DHOase is active in a trifunctional enzyme, CAD, which also carries out the activities of carbamoyl phosphate synthetase and aspartate transcarbamoylase. Prior to this study, it was unknown whether the FDA-approved clinical drug 5-fluorouracil (5-FU), which is used as an anticancer therapy, could bind to the DHOase domain of human CAD (huDHOase). Here, we identified huDHOase as a new 5-FU binding protein, thereby extending the 5-FU interactome to this human enzyme. In order to investigate where 5-FU binds to huDHOase, we solved the complexed crystal structure at 1.97 Å (PDB ID 8GVZ). The structure of huDHOase complexed with malate was also determined for the sake of comparison (PDB ID 8GW0). These two nonsubstrate ligands were bound at the active site of huDHOase. It was previously established that the substrate
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Registered trials
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