ReviewProtein science : a publication of the Protein Society2021
Deciphering CAD: Structure and function of a mega-enzymatic pyrimidine factory in health and disease.
Review in Protein science : a publication of the Protein Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Integrated multi-omics mapping of the causal landscape of gout across the circulating-tissue axis.Frontiers in immunology · 2026Pooled it
- Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase.Nature metabolism · 2026Article
- Genetic analysis of pyrimidine biosynthetic enzymes in Plasmodium falciparum.PLoS pathogens · 2026Article
- Genetic analysis of pyrimidine biosynthetic enzymes inbioRxiv : the preprint server for biology · 2025Article
- 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
- Epileptic encephalopathy in a young Bengal cat caused by CAD deficiency.Scientific reports · 2025Article
- Epileptic Encephalopathy Related to CAD Deleterious Variants-A Case Series.Diseases (Basel, Switzerland) · 2025Article
- The Loop-In Binding Mode of Dihydroorotase: Implications for Ligand Binding and Therapeutic Targeting.International journal of molecular sciences · 2025Review
- EGF-Upregulated lncRNA ESSENCE Promotes Colorectal Cancer Growth through Stabilizing CAD and Ferroptosis Defense.Research (Washington, D.C.) · 2025Article
- Prognostic value of nucleotide excision repair and translesion DNA synthesis proteins in muscle-infiltrating bladder carcinoma.BMC cancer · 2024Article
- Novel CAD gene mutations in a boy with developmental and epileptic encephalopathy 50 with dramatic response to uridine therapy: a case report and a review of the literature.BMC pediatrics · 2024Review
- Cytoophidia: a conserved yet promising mode of enzyme regulation in nucleotide metabolism.Molecular biology reports · 2024Review
- The emerging roles of glutamine amidotransferases in metabolism and immune defense.Nucleosides, nucleotides & nucleic acids · 2024Review
- Beyond genetics: Deciphering the impact of missense variants in CAD deficiency.Journal of inherited metabolic disease · 2023Article
- Cooperation is the key: the CCN biological system as a gate to high complex protein superfamilies' signaling.Journal of cell communication and signaling · 2023Article
- Article
- Complexed Crystal Structure of the Dihydroorotase Domain of Human CAD Protein with the Anticancer Drug 5-Fluorouracil.Biomolecules · 2023Article
- A Tailored Strategy to Crosslink the Aspartate Transcarbamoylase Domain of the Multienzymatic Protein CAD.Molecules (Basel, Switzerland) · 2023Article
- Sensitivities and Dependencies ofMedicina (Kaunas, Lithuania) · 2022Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CAD is a 1.5 MDa particle formed by hexameric association of a 250 kDa protein divided into different enzymatic domains, each catalyzing one of the initial reactions for de novo biosynthesis of pyrimidine nucleotides: glutaminase-dependent Carbamoyl phosphate synthetase, Aspartate transcarbamoylase, and Dihydroorotase. The pathway for de novo pyrimidine synthesis is essential for cell proliferation and is conserved in all living organisms, but the covalent linkage of the first enzymatic activities into a multienzymatic CAD particle is unique to animals. In other organisms, these enzymatic activities are encoded as monofunctional proteins for which there is abundant structural and biochemical information. However, the knowledge about CAD is scarce and fragmented. Understanding CAD requires not only to determine the three-dimensional structures and define the catalytic and regulatory mechanisms of the different enzymatic domains, but also to comprehend how these domains entangle and work in a coordinated and regulated manner. This review summarizes significant progress over the past 10 years toward the characterization of CAD's architecture, function, regulatory mechanisms, and cellular compartmentalization, as well as the recent finding of a new and rare neurometabolic disorder caused by defects in CAD activities.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.