4Q30

Nitrowillardiine bound to the ligand binding domain of GluA2 at pH 3.5

4Q30 の概要

• エントリーDOI: 10.2210/pdb4q30/pdb
• 関連するPDBエントリー: 3RTW
• 分子名称: Glutamate receptor 2 CHIMERIC PROTEIN, 3-(5-nitro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-L-alanine, ZINC ION, ... (4 entities in total)
• 機能のキーワード: glutamate receptor, glua2, glur2, ampa receptor, lbd, neurotransmitter receptor, nitrowillardiine, transport protein
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats); 詳細
• 細胞内の位置: Cell membrane; Multi-pass membrane protein: P19491
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 87481.46

構造登録者

Ahmed, A.H.,Oswald, R.E. (登録日: 2014-04-10, 公開日: 2014-06-04, 最終更新日: 2024-11-20)

主引用文献

Martinez, M.,Ahmed, A.H.,Loh, A.P.,Oswald, R.E.
Thermodynamics and mechanism of the interaction of willardiine partial agonists with a glutamate receptor: implications for drug development.
Biochemistry, 53:3790-3795, 2014

PubMed Abstract: Understanding the thermodynamics of binding of a lead compound to a receptor can provide valuable information for drug design. The binding of compounds, particularly partial agonists, to subtypes of the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor is, in some cases, driven by increases in entropy. Using a series of partial agonists based on the structure of the natural product, willardiine, we show that the charged state of the ligand determines the enthalpic contribution to binding. Willardiines have uracil rings with pKa values ranging from 5.5 to 10. The binding of the charged form is largely driven by enthalpy, while that of the uncharged form is largely driven by entropy. This is due at least in part to changes in the hydrogen bonding network within the binding site involving one water molecule. This work illustrates the importance of charge to the thermodynamics of binding of agonists and antagonists to AMPA receptors and provides clues for further drug discovery.

PubMed: 24850223
DOI: 10.1021/bi500511m

実験手法

X-RAY DIFFRACTION (2.03 Å)