8BW7
Cryo-EM structure of rat SLC22A6 bound to alpha-ketoglutaric acid
Summary for 8BW7
| Entry DOI | 10.2210/pdb8bw7/pdb |
| EMDB information | 16280 |
| Descriptor | Solute carrier family 22 member 6, Synthetic nanobody (Sybody), 2-OXOGLUTARIC ACID, ... (4 entities in total) |
| Functional Keywords | membrane protein, transporter |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 2 |
| Total formula weight | 76814.93 |
| Authors | Parker, J.L.,Kato, T.,Newstead, S. (deposition date: 2022-12-06, release date: 2023-07-19, Last modification date: 2024-11-13) |
| Primary citation | Parker, J.L.,Kato, T.,Kuteyi, G.,Sitsel, O.,Newstead, S. Molecular basis for selective uptake and elimination of organic anions in the kidney by OAT1. Nat.Struct.Mol.Biol., 30:1786-1793, 2023 Cited by PubMed Abstract: In mammals, the kidney plays an essential role in maintaining blood homeostasis through the selective uptake, retention or elimination of toxins, drugs and metabolites. Organic anion transporters (OATs) are responsible for the recognition of metabolites and toxins in the nephron and their eventual urinary excretion. Inhibition of OATs is used therapeutically to improve drug efficacy and reduce nephrotoxicity. The founding member of the renal organic anion transporter family, OAT1 (also known as SLC22A6), uses the export of α-ketoglutarate (α-KG), a key intermediate in the Krebs cycle, to drive selective transport and is allosterically regulated by intracellular chloride. However, the mechanisms linking metabolite cycling, drug transport and intracellular chloride remain obscure. Here, we present cryogenic-electron microscopy structures of OAT1 bound to α-KG, the antiviral tenofovir and clinical inhibitor probenecid, used in the treatment of Gout. Complementary in vivo cellular assays explain the molecular basis for α-KG driven drug elimination and the allosteric regulation of organic anion transport in the kidney by chloride. PubMed: 37482561DOI: 10.1038/s41594-023-01039-y PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.53 Å) |
Structure validation
Download full validation report
