Current Pharmaceutical Biotechnology - Volume 15, Issue 10, 2014

Signals relayed through G protein-coupled receptors (GPCR) play pivotal roles in human physiology and are important drug targets. About 40% of all GPCRs couple to the heterotrimeric G protein Gq. Biochemical studies as well as crystallography have improved our understanding of GqPCRs and their downstream partners. Here we focus on the "functional imaging" tools that have been developed to visualize, dissect and quan Read More

As the largest family of integral membrane proteins, G-protein-coupled receptors (GPCRs) comprise the largest class of therapeutic targets that aimed approximately 40% of modern medicinal drugs. Understanding the agonist/ antagonist mechanism, as well as the signal transduction of the GPCRs, is pivotal in drug discovery and new therapeutic strategy development. In the past few years, determination of high-resolution cr Read More

GPCRs are a major family of homologous proteins and are key mediators of the effects of numerous endogenous neurotransmitters, hormones, cytokines, therapeutic drugs, and drugs-of-abuse. Despite the enormous amount of research on the pharmacological and biochemical properties of GPCRs, there is surprisingly little information on GPCR dimer structure and function in primary cell culture or in vivo. We have used two n Read More

Chemokine receptors are G protein-coupled receptors that contain seven trans-membrane domains. CXCR4 and CCR5 as major co-receptors for HIV-1 entry into host cells are implicated in cancer and inflammation. They have been attractive targets for the pharmaceutical industry basing on their roles in HIV disease. Homology modeling, molecular docking, molecular dynamics, Molecular Mechanics/Generalized Born Surface Read More

Detection of tastes is critical for animals. Sweet, umami and bitter taste are mediated by G-protein-coupled receptors that are expressed in the taste receptor cells. TAS1Rs which belong to class C G-protein-coupled receptors form heterodimeric complexes to function as sweet (TAS1R2 + TAS1R3) or umami (TAS1R1 + TAS1R3) taste receptors. Umami taste is also considered to be mediated by mGluRs. TAS2Rs belong to cla Read More

G-protein-coupled receptors (GPCRs) represent the main family of cell surface receptors and are virtually expressed in all eukaryotic cells. Interestingly, a large number of clinically used drugs exert their pharmacological effect via a GPCR, thus it seems crucial to deeply understand the biology of these receptors. The study of GPCR activation and signaling has been classically performed by physiological, biochemical and Read More

G protein-coupled receptors (GPCRs), a family of seven-transmembrane receptors, are among the most important drug targets with over half of all marketed drugs targeting the family. However, only a handful of easily druggable GPCRs are successfully targeted by pharmaceuticals. Efforts to shift this intensive focus to other, more recalcitrant GPCR targets will increasingly draw on new information such as structural details, w Read More

G-protein coupled receptors (GPCRs) are proteins of the plasma membrane, which are characterized by seven membrane-spanning segments (TMs). GPCRs play an important role in almost all of our physiological and pathophysiological conditions by interacting with a large variety of ligands and stimulating different G-proteins and signaling cascades. By playing a key role in the function of our body and being involved in the p Read More

Kir3 (or GIRK) channels have been known for nearly three decades to be activated by direct interactions with the βγ subunits of heterotrimeric G (Gαβγ) proteins in a membrane-delimited manner. Gα also interacts with GIRK channels and since PTX-sensitive Gα subunits show higher affinity of interaction they confer signaling specificity to G Protein- Coupled Receptors (GPCRs) that normally couple to these G protein subunits. In Read More

Growing experimental evidences suggest that dimerization and oligomerization are important for G Protein- Coupled Receptors (GPCRs) function. The detailed structural information of dimeric/oligomeric GPCRs would be very important to understand their function. Although it is encouraging that recently several experimental GPCR structures in oligomeric forms have appeared, experimental determination of GPCR structures Read More