Structure-based design in the GPCR target space.
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.
Department of Pharmaceutical Sciences, Southern Illinois University Edwardsville, Edwardsville, IL 62026, USA. mkontoy@siue.edu
M
M
Kontoyianni
Z
Z
Liu
D000818:Animals; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism
D043562:Receptors, G-Protein-Coupled