ArticleNature communications2025
Mechanisms of urate transport and uricosuric drugs inhibition in human URAT1.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Polydatin alleviates adenine-induced nephropathy in mice.Renal failure · 2026Article
- Cryo-EM structures of Cdr1 reveal snapshots of substrate transport and diverse inhibitor recognition.Science advances · 2026Article
- Pomegranate Peel Polyphenol Extract Ameliorates Hyperuricemia by Inhibiting Uric Acid Synthesis and Reabsorption.Chemical biology & drug design · 2026Article
- Longitudinal serum uric acid transition patterns and their clinical, genetic, and dietary determinants: prospective prediction of incident hyperuricemia and gout in a Korean population-based cohort.Clinical rheumatology · 2026Article
- Gut microbiota-associated N-Acetyl-L-leucine mediates fructose-induced hyperuricemia via the P300-URAT1 pathway.NPJ science of food · 2026Article
- The Biobank Rare Variant consortium powers the discovery of rare genetic associations through global collaboration.medRxiv : the preprint server for health sciences · 2026Article
- Urate transporters: Structural mechanisms and therapeutic opportunities in drug development.Acta pharmaceutica Sinica. B · 2026Article
- Structural basis for prostaglandin and drug transport via SLCO2A1.Nature communications · 2026Article
- URAT1 inhibition in hyperuricemia and gout: from transporter biology to clinical precision therapy.Frontiers in immunology · 2026Review
- Comprehensive phytochemical profiling of dealcoholized zhuyeqing liquor extract and its protective effect on hyperuricemia by regulating urate transporters and LPS/NLRP3 inflammasome pathway.Frontiers in nutrition · 2026Article
- Extra-renal role of urate transporter-1 in diabetes.World journal of diabetes · 2025Review
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- Article
- Progress in animal models for studying hyperuricemia.Frontiers in pharmacology · 2025Review
- Mechanistic Study on the Therapeutic Effects of Juanbi Lijieqing Formula in a Rat Model of Gouty Arthritis with Hyperuricemia.Journal of pain research · 2025Article
- Comprehensive characterisation of the active ingredients ofFrontiers in pharmacology · 2025Article
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Authors and funding
7 authors.
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Abstract
High urate levels in circulation lead to the accumulation of urate crystals in joints and ultimately inflammation and gout. The reabsorption process of urate in the kidney by the urate transporter URAT1 plays a pivotal role in controlling serum urate levels. Pharmacological inhibition of URAT1 by uricosuric drugs is a valid strategy for gout management. Despite the clinical significance of URAT1, its structural mechanism and dynamics remain incompletely understood. Here, we report the structures of human URAT1 (hURAT1) in complex with substrate urate or inhibitors benzbromarone and verinurad at resolution ranges from 3.0 to 3.3 Å. We observe urate in the central substrate-binding site of hURAT1 in the outward-facing conformation and urate is wrapped in the center of hURAT1 by five phenylalanines and coordinated by two positively charged residues on each side. Uricosuric compounds benzbromarone and verinurad occupy the urate-binding site of hURAT1 in the inward-facing conformation. Structural comparison between different conformations of hURAT1 reveals the rocker-switch-like mechanism for urate transport. Benzbromarone and verinurad exert their inhibitory effect by blocking not only the binding of urate but also the structural isomerization of hURAT1.
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