4FY0

Crystal structure of LeuT-F253A bound to L-selenomethionine from lipid bicelles

4FY0 の概要

• エントリーDOI: 10.2210/pdb4fy0/pdb
• 関連するPDBエントリー: 4FXZ
• 分子名称: Transporter, SODIUM ION, SELENOMETHIONINE (3 entities in total)
• 機能のキーワード: amino acid transporter, transport protein
• 由来する生物種: Aquifex aeolicus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57618.67

構造登録者

Wang, H.,Gouaux, E. (登録日: 2012-07-03, 公開日: 2012-08-08, 最終更新日: 2024-02-28)

主引用文献

Wang, H.,Gouaux, E.
Substrate binds in the S1 site of the F253A mutant of LeuT, a neurotransmitter sodium symporter homologue.
Embo Rep., 13:861-866, 2012

PubMed Abstract: LeuT serves as the model protein for understanding the relationships between structure, mechanism and pharmacology in neurotransmitter sodium symporters (NSSs). At the present time, however, there is a vigorous debate over whether there is a single high-affinity substrate site (S1) located at the original, crystallographically determined substrate site or whether there are two high-affinity substrates sites, one at the primary or S1 site and the other at a second site (S2) located at the base of the extracellular vestibule. In an effort to address the controversy over the number of high-affinity substrate sites in LeuT, one group studied the F253A mutant of LeuT and asserted that in this mutant substrate binds exclusively to the S2 site and that 1 mM clomipramine entirely ablates substrate binding to the S2 site. Here we study the binding of substrate to the F253A mutant of LeuT using ligand binding and X-ray crystallographic methods. Both experimental methods unambiguously show that substrate binds to the S1 site of the F253A mutant and that binding is retained in the presence of 1 mM clomipramine. These studies, in combination with previous work, are consistent with a mechanism for LeuT that involves a single high-affinity substrate binding site.

PubMed: 22836580
DOI: 10.1038/embor.2012.110

実験手法

X-RAY DIFFRACTION (3 Å)