Analysis of the crystal structure of beta-2 adrenoceptors (β2ARs) is providing new insights into the functioning
of this receptor and perhaps of G-protein coupled receptors (GPCRs) as a whole. This class of receptors represents the target
of at least a third of the drugs on the market and plays an essential role in the study of therapetic drug-response.
Among GPCRs, the β2AR is the best understood in terms of function, expression and activation. Regarding the interaction
of β2ARs with a specific ligand, polymorphisms, conformational changes and stereoselectivity are important factors. Agonist
affinity for β2ARs is influenced by the polymorphisms of these receptors, which in some cases appear to affect susceptibility
to disorders. Conformational changes that take place upon the approach of a given ligand, as well as the stereoselectivity
of this class of receptors can modify the intrinsic activity of β2ARs (and certainly of other receptors as well).
Hence, a deepening understanding of these factors can provide new data on affinity and specifically the key residues involved
in recognition of β2AR agonists. The deepening the understanding of the factors involved in ligand affinity for
β2ARs will assist in the development of β2AR agonists that are more selective and potent, and that have longer term action.
Not only are β2AR agonists employed as therapeutic agents, but also in diagnosis. Currently, the main clinical application
of targeting human β2ARs is to treat asthma with bronchodilators. However, they are also used to treat other maladies
in their acute or chronic forms, including heart conditions, metabolic disorders and muscle wasting. This review
shows the scope and the possible future clinical implications of data from structures of β2ARs.
Keywords: Beta-2 adrenoceptor agonists, heart disorders, pulmonary diseases, structural biology, G-protein coupled receptors (GPCRs), β2AR, polymorphism, ligand affinity, therapeutic agent, cyclic adenosine monophosphate (cAMP).
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Published on: 02 August, 2012
Page: [1336 - 1346]