2Y58

Fragment growing induces conformational changes in acetylcholine- binding protein: A structural and thermodynamic analysis - (Compound 6)

2Y58 の概要

• エントリーDOI: 10.2210/pdb2y58/pdb
• 関連するPDBエントリー: 2BR7 2BR8 2BYN 2BYP 2BYQ 2BYR 2BYS 2C9T 2UZ6 2W8E 2W8F 2W8G 2WN9 2WNC 2WNJ 2WNL 2WZY 2X00 2XNT 2XNU 2XNV 2XYS 2XYT 2XZ5 2XZ6 2Y54 2Y56 2Y57
• 分子名称: SOLUBLE ACETYLCHOLINE RECEPTOR, [(1R,5S)-8-[(2R)-2-HYDROXY-2-PHENYL-ETHYL]-8-METHYL-8-AZONIABICYCLO[3.2.1]OCTAN-3-YL] BENZOATE, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: receptor
• 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: 125872.23

構造登録者

Rucktooa, P.,Edink, E.,deEsch, I.J.P.,Sixma, T.K. (登録日: 2011-01-12, 公開日: 2011-06-15, 最終更新日: 2023-12-20)

主引用文献

Edink, E.,Rucktooa, P.,Retra, K.,Akdemir, A.,Nahar, T.,Zuiderveld, O.,Van Elk, R.,Janssen, E.,Van Nierop, P.,Van Muijlwijk-Koezen, J.,Smit, A.B.,Sixma, T.K.,Leurs, R.,De Esch, I.J.P.
Fragment Growing Induces Conformational Changes in Acetylcholine-Binding Protein: A Structural and Thermodynamic Analysis.
J.Am.Chem.Soc., 133:5363-, 2011

PubMed Abstract: Optimization of fragment hits toward high-affinity lead compounds is a crucial aspect of fragment-based drug discovery (FBDD). In the current study, we have successfully optimized a fragment by growing into a ligand-inducible subpocket of the binding site of acetylcholine-binding protein (AChBP). This protein is a soluble homologue of the ligand binding domain (LBD) of Cys-loop receptors. The fragment optimization was monitored with X-ray structures of ligand complexes and systematic thermodynamic analyses using surface plasmon resonance (SPR) biosensor analysis and isothermal titration calorimetry (ITC). Using site-directed mutagenesis and AChBP from different species, we find that specific changes in thermodynamic binding profiles, are indicative of interactions with the ligand-inducible subpocket of AChBP. This study illustrates that thermodynamic analysis provides valuable information on ligand binding modes and is complementary to affinity data when guiding rational structure- and fragment-based discovery approaches.

PubMed: 21322593
DOI: 10.1021/JA110571R

実験手法

X-RAY DIFFRACTION (3.25 Å)