6TD2

Mus musculus Acetylcholinesterase in complex with N-(2-(diethylamino)ethyl)-1-(4-(trifluoromethyl)phenyl)methanesulfonamide

6TD2 の概要

• エントリーDOI: 10.2210/pdb6td2/pdb
• 分子名称: Acetylcholinesterase, 2-acetamido-2-deoxy-beta-D-glucopyranose, ~{N}-[2-(diethylamino)ethyl]-1-[4-(trifluoromethyl)phenyl]methanesulfonamide, ... (8 entities in total)
• 機能のキーワード: complex, inhibitor, hydrolase
• 由来する生物種: Mus musculus (House mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 122184.00

構造登録者

Forsgren, N.,Ekstrom, F. (登録日: 2019-11-07, 公開日: 2020-10-14, 最終更新日: 2024-10-23)

主引用文献

Andersson, C.D.,Mishra, B.K.,Forsgren, N.,Ekstrom, F.,Linusson, A.
Physical Mechanisms Governing Substituent Effects on Arene-Arene Interactions in a Protein Milieu.
J.Phys.Chem.B, 124:6529-6539, 2020

PubMed Abstract: Arene-arene interactions play important roles in protein-ligand complex formation. Here, we investigate the characteristics of arene-arene interactions between small organic molecules and aromatic amino acids in protein interiors. The study is based on X-ray crystallographic data and quantum mechanical calculations using the enzyme acetylcholinesterase and selected inhibitory ligands as a model system. It is shown that the arene substituents of the inhibitors dictate the strength of the interaction and the geometry of the resulting complexes. Importantly, the calculated interaction energies correlate well with the measured inhibitor potency. Non-hydrogen substituents strengthened all interaction types in the protein milieu, in keeping with results for benzene dimer model systems. The interaction energies were dispersion-dominated, but substituents that induced local dipole moments increased the electrostatic contribution and thus yielded more strongly bound complexes. These findings provide fundamental insights into the physical mechanisms governing arene-arene interactions in the protein milieu and thus into molecular recognition between proteins and small molecules.

PubMed: 32610016
DOI: 10.1021/acs.jpcb.0c03778

実験手法

X-RAY DIFFRACTION (2.8 Å)