ArticleCell research2024
Transport mechanism and structural pharmacology of human urate transporter URAT1.
Article in Cell research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Linking Hyperuricemia to Cancer: Emerging Evidence on Risk and Progression.Current oncology reports · 2025Pooled it
- 6'‑O‑Caffeoylarbutin attenuates experimental hyperuricemia by regulating renal and intestinal urate transport, intestinal barrier integrity, and gut microbiota.Molecular medicine reports · 2026Article
- Associations of Genetic Variants in Uric Acid Transporter Genes With Salt Sensitivity, Longitudinal Blood Pressure Changes, and Incident Hypertension in Chinese Adults.Journal of clinical hypertension (Greenwich, Conn.) · 2026Article
- Cryo-EM structures of Cdr1 reveal snapshots of substrate transport and diverse inhibitor recognition.Science advances · 2026Article
- Structure and mechanism of human sphingosine-1-phosphate transporter MFSD2B.Nature communications · 2026Article
- Gut microbiota-associated N-Acetyl-L-leucine mediates fructose-induced hyperuricemia via the P300-URAT1 pathway.NPJ science of food · 2026Article
- HIF-1α in CD4Journal of pharmaceutical analysis · 2026Article
- Urate transporters: Structural mechanisms and therapeutic opportunities in drug development.Acta pharmaceutica Sinica. B · 2026Article
- Advances in the management of gout: From current strategies to emerging therapies.The Journal of international medical research · 2026Review
- Structural basis for prostaglandin and drug transport via SLCO2A1.Nature communications · 2026Article
- Structure and mechanism of human sphingosine-1-phosphate transporter MFSD2B.bioRxiv : the preprint server for biology · 2026Article
- VARIDT 4.0: distribution variability of drug transporters.Nucleic acids research · 2026Article
- URAT1 inhibition in hyperuricemia and gout: from transporter biology to clinical precision therapy.Frontiers in immunology · 2026Review
- The roles of gut microbiota and their metabolites in uric acid-related metabolic diseases: mechanisms and therapeutic targets.Frontiers in microbiology · 2026Review
- Synteny - a high throughput web tool to streamline causal gene prioritisation and provide insight into protein function.Scientific reports · 2025Article
- Structural basis of sodium ion-dependent carnitine transport by OCTN2.Nature communications · 2025Article
- Structural pharmacology of SV2A reveals an allosteric modulation mechanism in the major facilitator superfamily.Nature communications · 2025Article
- Antihyperuricemic Effects ofInternational journal of molecular sciences · 2025Article
- Potential Transmembrane Proteins-transporters of Chelidonic Acid for its Intracellular Uptake: In Silico Simulation.Pharmaceutical research · 2025Article
- Discovery of multi-target anti-gout agents from Eurycoma longifolia Jack through phenotypic screening and structural optimization.Nature communications · 2025Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Urate is an endogenous product of purine metabolism in the liver. High urate levels in the blood lead to gout, a very common and painful inflammatory arthritis. Excreted urate is reabsorbed in the kidney mainly by URAT1 antiporter, a key target for anti-gout drugs. To uncover the mechanisms of urate transport and drug inhibition, we determined cryo-EM structures of human URAT1 with urate, counter anion pyrazinoate, or anti-gout drugs of different chemotypes - lesinurad, verinurad, and dotinurad. We captured the outward-to-inward transition of URAT1 during urate uptake, revealing that urate binds in a phenylalanine-rich pocket and engages with key gating residues to drive the transport cycle. In contrast to the single binding site for urate, pyrazinoate interacts with three distinct, functionally relevant sites within URAT1, a mechanism that has not yet been observed in other anion antiporters. In addition, we found that while all three drugs compete with substrates and halt the transport cycle, verinurad and dotinurad further hijack gating residues to achieve high potency. These insights advance our understanding of organic anion transport and provide a foundation for designing improved gout therapeutics.
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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.