6AWQ

Anomalous chloride signal reveals the position of sertraline complexed with the serotonin transporter at the central site

6AWQ の概要

• エントリーDOI: 10.2210/pdb6awq/pdb
• 分子名称: Sodium-dependent serotonin transporter, 8B6 antibody FAB heavy chain, 8B6 antibody FAB light chain, ... (8 entities in total)
• 機能のキーワード: neurotransmitter transporter, antidepressant, transport protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 111478.33

構造登録者

Coleman, J.A.,Gouaux, E. (登録日: 2017-09-06, 公開日: 2017-10-25, 最終更新日: 2023-10-04)

主引用文献

Coleman, J.A.,Gouaux, E.
Structural basis for recognition of diverse antidepressants by the human serotonin transporter.
Nat. Struct. Mol. Biol., 25:170-175, 2018

PubMed Abstract: Selective serotonin reuptake inhibitors are clinically prescribed antidepressants that act by increasing the local concentrations of neurotransmitters at synapses and in extracellular spaces via blockade of the serotonin transporter. Here we report X-ray structures of engineered thermostable variants of the human serotonin transporter bound to the antidepressants sertraline, fluvoxamine, and paroxetine. The drugs prevent serotonin binding by occupying the central substrate-binding site and stabilizing the transporter in an outward-open conformation. These structures explain how residues within the central site orchestrate binding of chemically diverse inhibitors and mediate transporter drug selectivity.

PubMed: 29379174
DOI: 10.1038/s41594-018-0026-8

実験手法

X-RAY DIFFRACTION (4.046 Å)