Assembly of a π-π Stack of ligands in the binding site of an acetylcholine-binding protein
| Autor: | 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 Titia, K., Sixma, T.K. |
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| Přispěvatelé: | Stornaiuolo, Mariano, and De Kloe, G. E., and Rucktooa, P., and Fish, A., and Van Elk, R., and Edink, E. S., and Bertrand, D., and Smit, A. B., and De Esch, I. J. P., and Sixma, T. K., Medicinal chemistry, Molecular and Cellular Neurobiology, AIMMS, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular General Physics and Astronomy Plasma protein binding protein binding supramolecular chemistry Acetylcholine Ligands Crystallography X-Ray 01 natural sciences Acetylcholine binding 0303 health sciences Multidisciplinary Chemistry Small molecule 3. Good health protein article Nicotinic agonist Biochemistry paradigm shift protein stability SDG 6 - Clean Water and Sanitation Acetylcholine medicine.drug Stereochemistry unclassified drug drug protein assembly Electrons binding protein Ligand 010402 general chemistry Electron Article General Biochemistry Genetics and Molecular Biology Fluorescence 03 medical and health sciences medicine Animals Molecule Binding site 030304 developmental biology Acetylcholine receptor Binding Sites binding site Animal General Chemistry acetylcholine Acridine Orange 0104 chemical sciences Carrier Proteins Carrier Protein acetylcholine binding protein |
| Zdroj: | 'Nature Communications ', vol: 4, pages: 1875-1-1875-11 (2013) Nature Communications, 4:1875. Nature Publishing Group Nature Communications Nature Communications; Vol 4 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 2013, ' Assembly of a π–π stack of ligands in the binding site of an acetylcholine-binding protein ', Nature Communications, vol. 4, 1875, pp. 1875 . https://doi.org/10.1038/ncomms2900 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms2900 |
| Popis: | 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. AChBP is used as a structurally accessible prototype for studying ligand binding to nicotinic acetylcholine receptors. Stornaiuolo et al. report that a small molecule binds AChBP in an ordered p–p stack of three molecules per binding site, which may lead to new approaches in drug design. |
| Databáze: | OpenAIRE |
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