9CY3

Outward-facing Atorvastatin-bound OATP1B1 with sybody Sb5

9CY3 の概要

• エントリーDOI: 10.2210/pdb9cy3/pdb
• EMDBエントリー: 46005
• 分子名称: Solute carrier organic anion transporter family member 1B1, Sybody 5, 7-[2-(4-FLUORO-PHENYL)-5-ISOPROPYL-3-PHENYL-4-PHENYLCARBAMOYL-PYRROL-1-YL]- 3,5-DIHYDROXY-HEPTANOIC ACID (3 entities in total)
• 機能のキーワード: solute carrier, sybody, membrane protein, drug-drug interactions, transport protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 96325.13

構造登録者

Sung, M.W.,Lees, J.A.,Han, S. (登録日: 2024-08-01, 公開日: 2025-04-16, 最終更新日: 2025-05-14)

主引用文献

Sung, M.W.,Hu, K.,Hurlimann, L.M.,Lees, J.A.,Fennell, K.F.,West, M.A.,Costales, C.,Rodrigues, A.D.,Zimmermann, I.,Dawson, R.J.P.,Liu, S.,Han, S.
Cyclosporine A sterically inhibits statin transport by solute carrier OATP1B1.
J.Biol.Chem., 301:108484-108484, 2025

PubMed Abstract: Members of the Organic Anion Transporter Polypeptides (OATP) are integral membrane proteins responsible for facilitating the transport of organic anions across the cell membrane. OATP1B1 (SLCO1B1), the prototypic OATP family member, is the most abundant uptake transporter in the liver and a key mediator of the hepatic uptake and clearance of numerous endogenous and xenobiotic compounds. It serves as a locus of important drug-drug interactions, such as those between statins and cyclosporine A, and carries the potential to enable liver-targeting therapeutics. In this study, we report cryo-EM structures of OATP1B1 and its complexes with one of its statin substrates, atorvastatin, and an inhibitor, cyclosporine A. This structural analysis has yielded insights into the mechanisms underlying the OATP1B1-mediated transport of statins and the inhibitory effect of cyclosporine A. These findings contribute to a better understanding of the molecular processes involved in drug transport and offer potential avenues for the development of targeted medications for liver-related conditions.

PubMed: 40199401
DOI: 10.1016/j.jbc.2025.108484

実験手法

ELECTRON MICROSCOPY (3.2 Å)