Selective binding of choline by a phosphate-coordination-based triple helicate featuring an aromatic box

• Published in: Nature communications Vol. 8; no. 1; pp. 938 - 8
• Main Authors: Jia, Chuandong, Zuo, Wei, Yang, Dong, Chen, Yanming, Cao, Liping, Custelcean, Radu, Hostaš, Jiří, Hobza, Pavel, Glaser, Robert, Wang, Yao-Yu, Yang, Xiao-Juan, Wu, Biao
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 16.10.2017; Nature Publishing Group UK; Nature Portfolio
• Subjects: Acetylcholine; Acetylcholine - chemistry; Acetylcholine - metabolism; Anions; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Binding Sites; Binding, Competitive; Biomimetics; Carnitine; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Chemistry; Choline; Choline - chemistry; Choline - metabolism; Choline-binding protein; Competition; Complementarity; Crystal structure; Crystallography, X-Ray; Density functional theory; Fluorescence; Glycine; Glycine betaine; Holes; Hydrogen bonds; INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Kinetics; Laboratories; Ligands; Membrane Transport Proteins - chemistry; Membrane Transport Proteins - metabolism; Models, Molecular; NMR; Nuclear magnetic resonance; Phosphates; Phosphates - chemistry; Phosphates - metabolism; Protein Binding; Protein Domains; Proteins; Proton Magnetic Resonance Spectroscopy; Receptors; Selective binding; Selectivity; Self-assembly; Shape recognition; Sinorhizobium meliloti - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-00915-8

In nature, proteins have evolved sophisticated cavities tailored for capturing target guests selectively among competitors of similar size, shape, and charge. The fundamental principles guiding the molecular recognition, such as self-assembly and complementarity, have inspired the development of biomimetic receptors. In the current work, we report a self-assembled triple anion helicate (host 2) featuring a cavity resembling that of the choline-binding protein ChoX, as revealed by crystal and density functional theory (DFT)-optimized structures, which binds choline in a unique dual-site-binding mode. This similarity in structure leads to a similarly high selectivity of host 2 for choline over its derivatives, as demonstrated by the NMR and fluorescence competition experiments. Furthermore, host 2 is able to act as a fluorescence displacement sensor for discriminating choline, acetylcholine, L-carnitine, and glycine betaine effectively.The choline-binding protein ChoX exhibits a synergistic dual-site binding mode that allows it to discriminate choline over structural analogues. Here, the authors design a biomimetic triple anion helicate receptor whose selectivity for choline arises from a similar binding mechanism.