Structure-Function Analysis of the  -Adrenergic Receptor

A major goal of medicinal chemistry and pharmacology is to understand the molecular basis for the interactions of drugs with their targets. Many drugs act by binding to specific cell-surface receptors, either as agonists, which stimulate receptor function, or as antagonists, which block the action of endogenous agonists. In recent years, it has become clear that cell-surface receptors can be classified into groups on the basis of their ligand-binding characteristics, their mechanisms of signal transduction, and their structural properties (Dixon et al. 1988). One such class of receptors, which binds small molecule or peptide hormones and neurotransmitters, couples through guanine-nucleotide-binding regulatory proteins (G proteins) to modulate the intracellular levels of a variety of second-messenger molecules (Fig. 1). On binding agonists, receptors of this class catalyze the exchange of a bound GDP molecule for GTP on one of several G proteins in the cell membrane. Most receptors appear to associate with...