7ZHA

Structure of human OCT3 in complex with inhibitor decynium-22

7ZHA の概要

• エントリーDOI: 10.2210/pdb7zha/pdb
• EMDBエントリー: 14728
• 分子名称: Solute carrier family 22 member 3, 1-ethyl-2-[(1-ethylquinolin-2-yl)methyl]quinoline (2 entities in total)
• 機能のキーワード: organic cation transporter, major-facilitator superfamily, slc22 family, corticosterone sensitive protein, membrane transport, decynium-22, membrane 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: 61661.29

構造登録者

Khanppnavar, B.,Korkhov, V. (登録日: 2022-04-05, 公開日: 2022-11-09, 最終更新日: 2024-10-16)

主引用文献

Khanppnavar, B.,Maier, J.,Herborg, F.,Gradisch, R.,Lazzarin, E.,Luethi, D.,Yang, J.W.,Qi, C.,Holy, M.,Jantsch, K.,Kudlacek, O.,Schicker, K.,Werge, T.,Gether, U.,Stockner, T.,Korkhov, V.M.,Sitte, H.H.
Structural basis of organic cation transporter-3 inhibition.
Nat Commun, 13:6714-6714, 2022

PubMed Abstract: Organic cation transporters (OCTs) facilitate the translocation of catecholamines, drugs and xenobiotics across the plasma membrane in various tissues throughout the human body. OCT3 plays a key role in low-affinity, high-capacity uptake of monoamines in most tissues including heart, brain and liver. Its deregulation plays a role in diseases. Despite its importance, the structural basis of OCT3 function and its inhibition has remained enigmatic. Here we describe the cryo-EM structure of human OCT3 at 3.2 Å resolution. Structures of OCT3 bound to two inhibitors, corticosterone and decynium-22, define the ligand binding pocket and reveal common features of major facilitator transporter inhibitors. In addition, we relate the functional characteristics of an extensive collection of previously uncharacterized human genetic variants to structural features, thereby providing a basis for understanding the impact of OCT3 polymorphisms.

PubMed: 36344565
DOI: 10.1038/s41467-022-34284-8

実験手法

ELECTRON MICROSCOPY (3.55 Å)