9J02

cryo-EM structure of apo hOAT1

9J02 の概要

• エントリーDOI: 10.2210/pdb9j02/pdb
• EMDBエントリー: 61046
• 分子名称: Solute carrier family 22 member 6 (1 entity in total)
• 機能のキーワード: transporter, organic anion, uptake, renal pathophysiology, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 61869.03

構造登録者

Yang, D.X.,Luo, Y.B. (登録日: 2024-08-02, 公開日: 2025-08-13, 最終更新日: 2026-02-18)

主引用文献

Wu, X.,Luo, Y.,Feng, S.,Ma, H.,Ke, B.,Wang, K.,Su, Z.,Yang, D.
Structures and membrane interactions of human OAT1 in complex with clinical used drugs.
Sci Adv, 11:eads5405-eads5405, 2025

PubMed Abstract: Organic anion transporters (OATs) in mammals mediate the renal excretion of numerous structurally diverse organic anionic compounds. Therapeutically inhibiting OATs has emerged as a strategy to modulate the elimination or retention of these substrates. Among them, OAT1 plays a pivotal role in the pharmacokinetics and drug-drug interactions of a wide range of prescription medications. Despite extensive structural investigations, the molecular structure, and basis of polyspecific anionic drug recognition of human OAT1 (hOAT1) have remained elusive. Here, we present cryogenic electron microscopy structures of hOAT1 and its complexes with the antiviral drug cidofovir and an FDA-approved type II diabetes medication glibenclamide, respectively. Our findings reveal that both cidofovir and glibenclamide bind to a central binding site, capturing the transporter in inward-facing conformations. These structures elucidate how specific residues within the central site orchestrate the binding of chemically diverse inhibitors and provide a structural basis for the drug recognition mechanism of hOAT1.

PubMed: 39951534
DOI: 10.1126/sciadv.ads5405

実験手法

ELECTRON MICROSCOPY (3.36 Å)