Abstract
G Protein-Coupled Receptors (GPCRs) are the most targeted group of proteins for the development of therapeutic drugs. Until the last decade, structural information about this family of membrane proteins was relatively scarce, and their mechanisms of ligand binding and signal transduction were modeled on the assumption that GPCRs existed and functioned as monomeric entities. New crystal structures of native and engineered GPCRs, together with important biochemical and biophysical data that reveal structural details of the activation mechanism(s) of this receptor family, provide a valuable framework to improve dynamic molecular models of GPCRs with the ultimate goal of elucidating their allostery and functional selectivity. Since the dynamic movements of single GPCR protomers are likely to be affected by the presence of neighboring interacting subunits, oligomeric arrangements should be taken into account to improve the predictive ability of computer-assisted structural models of GPCRs for effective use in drug design.
Keywords: GPCRs, molecular modeling, dynamics, activation, dimerization, oligomerization
Current Pharmaceutical Design
Title: Progress in Elucidating the Structural and Dynamic Character of G Protein-Coupled Receptor Oligomers for Use in Drug Discovery
Volume: 15 Issue: 35
Author(s): A. Bortolato, J. C. Mobarec, D. Provasi and M. Filizola
Affiliation:
Keywords: GPCRs, molecular modeling, dynamics, activation, dimerization, oligomerization
Abstract: G Protein-Coupled Receptors (GPCRs) are the most targeted group of proteins for the development of therapeutic drugs. Until the last decade, structural information about this family of membrane proteins was relatively scarce, and their mechanisms of ligand binding and signal transduction were modeled on the assumption that GPCRs existed and functioned as monomeric entities. New crystal structures of native and engineered GPCRs, together with important biochemical and biophysical data that reveal structural details of the activation mechanism(s) of this receptor family, provide a valuable framework to improve dynamic molecular models of GPCRs with the ultimate goal of elucidating their allostery and functional selectivity. Since the dynamic movements of single GPCR protomers are likely to be affected by the presence of neighboring interacting subunits, oligomeric arrangements should be taken into account to improve the predictive ability of computer-assisted structural models of GPCRs for effective use in drug design.
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Bortolato A., Mobarec C. J., Provasi D. and Filizola M., Progress in Elucidating the Structural and Dynamic Character of G Protein-Coupled Receptor Oligomers for Use in Drug Discovery, Current Pharmaceutical Design 2009; 15 (35) . https://dx.doi.org/10.2174/138161209789824768
DOI https://dx.doi.org/10.2174/138161209789824768 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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