NUCLEAR-MAGNETIC-RESONANCE (NMR) ANALYSIS OF LIGAND-RECEPTOR INTERACTIONS - THE CHOLINERGIC SYSTEM - A MODEL

Elucidation of the molecular mechanisms that govern ligand-receptor re cognition is essential to the rational design of specific pharmacologi cal reagents. Whereas often the receptor and its binding site are the target of investigation, study of the ligand in its free and bound sta te can also reveal important information regarding this recognition pr ocess. Nuclear magnetic resonance (NMR) spectroscopy can be extremely useful for such studies. In this review, we discuss the attributes of NMR in the study of ligand receptor interactions. The cholinergic rece ptor and its binding to the neurotransmitter, acetylcholine, and choli nerpic antagonists serve as a model system, illustrating the power of ligand analysis by NMR. The results discussed prove that the region of residues a 180-205 of the nicotinic acetylcholine receptor are an ess ential component of the cholinergic binding site and that ligand bindi ng involves a positively charged hydrophobic motif.