Abstract
The G protein-coupled receptors (GPCRs) are membrane proteins that transmit signals via G-protein coupling. They have long been the target of small molecule therapeutics accounting for 30% of the launched drug targets. They are subdivided into several classes, with rhodopsins corresponding to the largest class. Furthermore, a high number of new rhodopsin-like GPCR proteins are included in the druggable genome, thus they are projected to continue being of value to the pharmaceutical and biotechnology sectors. We present a comprehensive review of the structural information pertaining to GPCRs, in light of the most recently deposited crystal structures, along with comparisons of the available to-date structures at different activation states. Finally, computational approaches to GPCR modeling are discussed in conjunction with critical perspectives regarding feasibility and limitations.
Keywords: G-protein Coupled Receptors, Homology Modeling, Virtual Screening, Model-Building, Critical Assessment of Structure Prediction, Docking, Structure-Based Drug Design, Activation Mechanism, Conserved Motifs, Mutagenesis
Current Medicinal Chemistry
Title: Structure-Based Design in the GPCR Target Space
Volume: 19 Issue: 4
Author(s): M. Kontoyianni and Z. Liu
Affiliation:
Keywords: G-protein Coupled Receptors, Homology Modeling, Virtual Screening, Model-Building, Critical Assessment of Structure Prediction, Docking, Structure-Based Drug Design, Activation Mechanism, Conserved Motifs, Mutagenesis
Abstract: The G protein-coupled receptors (GPCRs) are membrane proteins that transmit signals via G-protein coupling. They have long been the target of small molecule therapeutics accounting for 30% of the launched drug targets. They are subdivided into several classes, with rhodopsins corresponding to the largest class. Furthermore, a high number of new rhodopsin-like GPCR proteins are included in the druggable genome, thus they are projected to continue being of value to the pharmaceutical and biotechnology sectors. We present a comprehensive review of the structural information pertaining to GPCRs, in light of the most recently deposited crystal structures, along with comparisons of the available to-date structures at different activation states. Finally, computational approaches to GPCR modeling are discussed in conjunction with critical perspectives regarding feasibility and limitations.
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Cite this article as:
Kontoyianni M. and Liu Z., Structure-Based Design in the GPCR Target Space, Current Medicinal Chemistry 2012; 19 (4) . https://dx.doi.org/10.2174/092986712798918824
DOI https://dx.doi.org/10.2174/092986712798918824 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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