8BVT

Cryo-EM structure of rat SLC22A6 bound to probenecid

8BVT の概要

• エントリーDOI: 10.2210/pdb8bvt/pdb
• EMDBエントリー: 16271
• 分子名称: Solute carrier family 22 member 6, Synthetic nanobody (Sybody), 4-(dipropylsulfamoyl)benzoic acid (3 entities in total)
• 機能のキーワード: membrane protein, transporter
• 由来する生物種: Rattus norvegicus (Christmas Island rat); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 76918.74

構造登録者

Parker, J.L.,Kato, T.,Newstead, S. (登録日: 2022-12-06, 公開日: 2023-07-19, 最終更新日: 2024-10-23)

主引用文献

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

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: 37482561
DOI: 10.1038/s41594-023-01039-y

実験手法

ELECTRON MICROSCOPY (3.94 Å)