5OAN

Crystal structure of mutant AChBP in complex with glycine (T53F, Q74R, Y110A, I135S, G162E, S206CCP_KGTG)

5OAN の概要

• エントリーDOI: 10.2210/pdb5oan/pdb
• 分子名称: Soluble acetylcholine receptor, CHLORIDE ION, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: receptor, acetylcholine binding, signaling protein
• 由来する生物種: Aplysia californica (California sea hare)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 142321.15

構造登録者

Dawson, A.,Hunter, W.N.,de Souza, J.O.,Trumper, P. (登録日: 2017-06-23, 公開日: 2018-08-08, 最終更新日: 2024-10-23)

主引用文献

Dawson, A.,Trumper, P.,de Souza, J.O.,Parker, H.,Jones, M.J.,Hales, T.G.,Hunter, W.N.
Engineering a surrogate human heteromeric alpha / beta glycine receptor orthosteric site exploiting the structural homology and stability of acetylcholine-binding protein.
Iucrj, 6:1014-1023, 2019

PubMed Abstract: Protein-engineering methods have been exploited to produce a surrogate system for the extracellular neurotransmitter-binding site of a heteromeric human ligand-gated ion channel, the glycine receptor. This approach circumvents two major issues: the inherent experimental difficulties in working with a membrane-bound ion channel and the complication that a heteromeric assembly is necessary to create a key, physiologically relevant binding site. Residues that form the orthosteric site in a highly stable ortholog, acetylcholine-binding protein, were selected for substitution. Recombinant proteins were prepared and characterized in stepwise fashion exploiting a range of biophysical techniques, including X-ray crystallography, married to the use of selected chemical probes. The decision making and development of the surrogate, which is termed a glycine-binding protein, are described, and comparisons are provided with wild-type and homomeric systems that establish features of molecular recognition in the binding site and the confidence that the system is suited for use in early-stage drug discovery targeting a heteromeric α/β glycine receptor.

PubMed: 31709057
DOI: 10.1107/S205225251901114X

実験手法

X-RAY DIFFRACTION (2.6 Å)