ArticleNature structural & molecular biology2023
The substrate and inhibitor binding mechanism of polyspecific transporter OAT1 revealed by high-resolution cryo-EM.
Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Gene-environment interaction modifies the association between hyperinsulinemia and serum urate levels through SLC22A12.The Journal of clinical investigation · 2025Trial
- Conformational cycling of the Wntless transporter drives trafficking and secretion of Wnt morphogens.Nature communications · 2026Article
- Urate transporters: Structural mechanisms and therapeutic opportunities in drug development.Acta pharmaceutica Sinica. B · 2026Article
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- Multitargeting Pt(IV) Anticancer Prodrugs Bearing Mono- and Bis-Probenecid Ligands in Axial Positions: Synthesis and Evaluation of Biological Activity.Pharmaceuticals (Basel, Switzerland) · 2026Article
- An Ex Vivo Patient-Derived Tumor-Bearing Human Kidney Model Recapitulates Drug Toxicity and Metabolic Distribution.Research (Washington, D.C.) · 2026Article
- Energetic and structural control of polyspecificity in a multidrug transporter.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structural mechanism of mRNA decoding by mammalian GTPase GTPBP1.Nature communications · 2025Article
- Structural basis of sodium ion-dependent carnitine transport by OCTN2.Nature communications · 2025Article
- Serine encodes drug selectivity in human OAT1.Structure (London, England : 1993) · 2025Article
- A direct solubilization approach to purify active full-length human neuropathy target esterase.Protein expression and purification · 2025Article
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- Structural mechanism of mRNA decoding by mammalian GTPase GTPBP1.bioRxiv : the preprint server for biology · 2025Article
- Structure and transport mechanism of the human prostaglandin transporter SLCO2A1.Nature communications · 2025Article
- Molecular basis of the urate transporter URAT1 inhibition by gout drugs.Nature communications · 2025Article
- Single-particle cryogenic electron microscopy structure determination for membrane proteins.Current opinion in structural biology · 2025Review
- Cyclosporine A sterically inhibits statin transport by solute carrier OATP1B1.The Journal of biological chemistry · 2025Article
- Understanding, inhibiting, and engineering membrane transporters with high-throughput mutational screens.Cell chemical biology · 2025Review
- Molecular mechanisms of urate transport by the native human URAT1 and its inhibition by anti-gout drugs.Cell discovery · 2025Article
- Molecular basis of the functional conflict between chloroquine and peptide transport in the Malaria parasite chloroquine resistance transporter PfCRT.Nature communications · 2025Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Organic anion transporters (OATs) of the SLC22 family have crucial roles in the transport of organic anions, including metabolites and therapeutic drugs, and in transporter-mediated drug-drug interactions. In the kidneys, OATs facilitate the elimination of metabolic waste products and xenobiotics. However, their transport activities can lead to the accumulation of certain toxic compounds within cells, causing kidney damage. Moreover, OATs are important drug targets, because their inhibition modulates the elimination or retention of substrates linked to diseases. Despite extensive research on OATs, the molecular basis of their substrate and inhibitor binding remains poorly understood. Here we report the cryo-EM structures of rat OAT1 (also known as SLC22A6) and its complexes with para-aminohippuric acid and probenecid at 2.1, 2.8 and 2.9 Å resolution, respectively. Our findings reveal a highly conserved substrate binding mechanism for SLC22 transporters, wherein four aromatic residues form a cage to accommodate the polyspecific binding of diverse compounds.
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