4BFQ

Assembly of a triple pi-stack of ligands in the binding site of Aplysia californica acetylcholine binding protein (AChBP)

Summary for 4BFQ

• Entry DOI: 10.2210/pdb4bfq/pdb
• Descriptor: SOLUBLE ACETYLCHOLINE RECEPTOR, 4,6-dimethyl-N'-(3-pyridin-2-ylisoquinolin-1-yl)pyrimidine-2-carboximidamide, GLYCEROL, ... (4 entities in total)
• Functional Keywords: receptor, acetylcholine binding protein, nicotinic acetylcholine receptor, cys-loop receptor, nachr, ion channel, pi-stacking, triple ligand binding, drug design
• Biological source: APLYSIA CALIFORNICA (CALIFORNIA SEA HARE)
• Total number of polymer chains: 5
• Total formula weight: 128496.70

Authors

Stornaiuolo, M.,De Kloe, G.E.,Rucktooa, P.,Fish, A.,van Elk, R.,Edink, E.S.,Bertrand, D.,Smit, A.B.,de Esch, I.J.P.,Sixma, T.K. (deposition date: 2013-03-21, release date: 2013-05-22, Last modification date: 2024-11-06)

Primary citation

Stornaiuolo, M.,De Kloe, G.E.,Rucktooa, P.,Fish, A.,van Elk, R.,Edink, E.S.,Bertrand, D.,Smit, A.B.,de Esch, I.J.P.,Sixma, T.K.
Assembly of a Pi-Pi Stack of Ligands in the Binding Site of an Acetylcholine Binding Protein
Nat.Commun., 4:1875-, 2013

PubMed Abstract: Acetylcholine-binding protein is a water-soluble homologue of the extracellular ligand-binding domain of cys-loop receptors. It is used as a structurally accessible prototype for studying ligand binding to these pharmaceutically important pentameric ion channels, in particular to nicotinic acetylcholine receptors, due to conserved binding site residues present at the interface between two subunits. Here we report that an aromatic conjugated small molecule binds acetylcholine-binding protein in an ordered π-π stack of three identical molecules per binding site, two parallel and one antiparallel. Acetylcholine-binding protein stabilizes the assembly of the stack by aromatic contacts. Thanks to the plasticity of its ligand-binding site, acetylcholine-binding protein can accommodate the formation of aromatic stacks of different size by simple loop repositioning and minimal adjustment of the interactions. This type of supramolecular binding provides a novel paradigm in drug design.

PubMed: 23695669
DOI: 10.1038/NCOMMS2900

Experimental method

X-RAY DIFFRACTION (2.4 Å)