Download or read book Identification of Candidate G Protein coupled Receptors written by Gayathri Viswanathan and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Identification of Candidate G Protein coupled Receptors written by Gayathri Viswanathan and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The G Protein Coupled Receptors Handbook written by Lakshmi A. Devi and published by Springer Science & Business Media. This book was released on 2008-03-01 with total page 414 pages. Available in PDF, EPUB and Kindle. Book excerpt: A comprehensive survey of the many recent advances in the field of G protein-coupled receptors (GPCR). The authors describe the current knowledge of GPCR receptor structure and function, the different mechanisms involved in the regulation of GPCR function, and the role of pharmacological chaperones in GPCR folding and maturation. They also present new findings about how GPCR dimerization/oligomerization modifies the properties of individual receptors and show how recent developments are leading to significant advances in drug discovery, such as the detection of ligands for orphan GPCRs. Also discussed are the most recent developments that could lead to new drug discoveries: the role of GPCRs in mediating pain, the development of receptor-type selective drugs based on the structural plasticity of receptor activation, and the identification of natural ligands of orphan GPCRs (deorphanization) as possible drug targets.
Download or read book Identification and Expression of G Protein Coupled Receptors written by Kevin R. Lynch and published by John Wiley & Sons. This book was released on 1999-05-10 with total page 246 pages. Available in PDF, EPUB and Kindle. Book excerpt: The past decade has seen tremendous advances in the study of G protein-coupled receptors (GPCRs), including the molecular cloning and identification of more than 100 hundred GPCR genes. But while GPCRs serve as targets for more than 300 medicines in the modern pharmacopoeia, the shrinking pool of known ligands and the continuing discovery of orphan GPCR genes have underscored the need for new approaches to ligand identification. Identification and Expression of G Protein-Coupled Receptors addresses this new direction in GPCR biochemistry-offering a definitive laboratory bench manual that emphasizes expression over primary cloning strategies. In a series of expert contributions by well-known researchers, this book provides detailed protocols for various expression systems-from bacteria to mammalian cells-as well as straightforward opinions on the advantages and shortcomings of each approach. Topics covered include: * Homology screening and the polymerase chain reaction in the cloning of GPCR genes * Cloning of GPCRs using mammalian cell expression * GPCR informatics and the orphan problem * The use of Xenopus laevis oocytes for the study of GPCRs * Stable expression of GPCRs in mammalian cells * Heterologous expression in primary cell cultures * Expression of GPCR in Escherichia coli * Large scale expression and purification of GPCRs in mammalian cells * High-level expression of GPCRs in the Baculovirus/Sf9 cell expression system * Expression of GPCRs in Drosophila Schneider 2 cells * Methods for genetic analysis and ligand identification using heterologous GPCRs expressed in Saccharomyces cerevisiae Supplemented with numerous photographs and illustrations, Identification and Expression of G Protein-Coupled Receptors is important reading for biochemists, pharmacologists, neuroscientists, structural biologists, and anyone involved in GPCR-based research. It delivers a wealth of useful advice, practical tips, and invaluable insight into trends at the cutting-edge of current research.
Download or read book G Protein Coupled Receptor Signaling in Plants written by Mark P. Running and published by Humana. This book was released on 2016-08-23 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Remarkably, while G protein-coupled receptors (GPCRs) are highly prevalent in animals and yeast, very few candidate GPCRs have been identified in plants. In G Protein-Coupled Receptor Signaling in Plants: Methods and Protocols, experts in the field describe techniques used in the study of small GTPases and related proteins. Beginning with a chapter on bioinformatics approaches for GPCR discovery, this detailed volume continues with chapters on heterotrimeric G protein subunits, Rab-GTPases, as well as lipid modifications, including myristoylation, acylation, and prenylation. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Practical and dependable, G Protein-Coupled Receptor Signaling in Plants: Methods and Protocols aims to aid further studies into the roles of small GTPases which will help elucidate numerous key processes in plants.
Download or read book G Protein Coupled Receptors written by Jesus Giraldo and published by Royal Society of Chemistry. This book was released on 2011-08-16 with total page 549 pages. Available in PDF, EPUB and Kindle. Book excerpt: G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors, with more than 800 members identified thus far in the human genome. They regulate the function of most cells in the body, and represent approximately 3% of the genes in the human genome. These receptors respond to a wide variety of structurally diverse ligands, ranging from small molecules, such as biogenic amines, nucleotides and ions, to lipids, peptides, proteins, and even light. Ligands (agonists and antagonists) acting on GPCRs are important in the treatment of numerous diseases, including cardiovascular and mental disorders, retinal degeneration, cancer, and AIDS. It is estimated that these receptors represent about one third of the actual identified targets of clinically used drugs. The determination of rhodopsin crystal structure and, more recently, of opsin, 1 and 2 adrenergic and A2A adenosine receptors provides both academia and industry with extremely valuable data for a better understanding of the molecular determinants of receptor function and a more reliable rationale for drug design. GPCR structure and function constitutes a hot topic. The book, which lies between the fields of chemical biology, molecular pharmacology and medicinal chemistry, is divided into three parts. The first part considers what receptor structures tell us about the mechanism of receptor activation. Part II focuses on receptor function. It discusses what the data from biophysical and mutational studies, and the analysis of the interactions of the receptor with ligands and regulator proteins, tell us about the process of signal transduction. The final part, on modelling and simulation, details new insights on the link between structure and mechanism and their implications in drug design.
Download or read book G Protein Coupled Receptors in Drug Discovery written by Kenneth H. Lundstrom and published by CRC Press. This book was released on 2005-07-11 with total page 376 pages. Available in PDF, EPUB and Kindle. Book excerpt: The broad range of G protein-coupled receptors (GPCRs) encompasses all areas of modern medicine and have an enormous impact on the process of drug development. Using disease-oriented methods to cover everything from screening to expression and crystallization, G Protein-Coupled Receptors in Drug Discovery describes the physiological roles of GPCRs
Download or read book Pharmacology of G Protein Coupled Receptors written by Richard R. Neubig and published by Academic Press. This book was released on 2011-09-19 with total page 408 pages. Available in PDF, EPUB and Kindle. Book excerpt: G protein coupled receptors remain the most important class of therapeutic targets in medicine. In the last 5 years, tremendous advances have been made in our understanding of the structure and mechanism of this critical family of drug targets. The present volume explores the modern experimental and conceptual framework for drug discovery for G protein coupled receptors. It explores advances in structure determination and structure-based drug design as well as new concepts of allosteric modulation, functional selectivity/biased agonism, and pharmacological chaperones. In addition, emerging drug targets such as receptor families for fatty acids, carboxylic acids, lipid mediators, etc. are included. Final chapters cover novel mechanisms of signal regulation through PDZ domains and RGS proteins. This volume will bring an up-to-date perspective on the G protein coupled receptor field to both academic and industry scientists. The present volume explores the modern experimental and conceptual framework for drug discovery for G protein coupled receptors It explores advances in structure determination and structure-based drug design as well as new concepts of allosteric modulation, functional selectivity/biased agonism, and pharmacological chaperones This volume will bring an up-to-date perspective on the G protein coupled receptor field to both academic and industry scientists
Download or read book Identification and Characterization of Th G Protein Coupled Receptors GPR100 Homo Sapiens and SALPR Mus Musculus written by Katrin Boels and published by Tenea Verlag Ltd.. This book was released on 2005 with total page 66 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book G Protein Coupled Receptor Screening Assays written by Sofia Aires M. Martins and published by Humana. This book was released on 2021-06-05 with total page 327 pages. Available in PDF, EPUB and Kindle. Book excerpt: This fully updated edition targets not only those assays directly involved in the discovery of GPCR-active compounds but also those involved in cell-based experiments designed to study physiological responses. Whether coming from academia or industry, or being an experienced researcher or a newcomer to the field, the reader will find accessible methods and protocols that cover the latest developments on receptor purification, molecular biology, recombinant engineering, and analytical techniques that enable the real time monitoring of the complex GPCR signaling cascade and identification of potential drug targets. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, G Protein-Coupled Receptor Screening Assays: Methods and Protocols, Second Edition aims to provide the tools necessary to contribute to the advancement of GPCR research and discovery and ultimately lead to the availability of innovative and more efficient drugs.
Download or read book Computer aided High throughput Screening for the Discovery of GPCR Biased Ligands written by Yu Xu (Researcher in bioengineering) and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: G protein-coupled receptors (GPCRs) constitute the largest family of membrane receptors in the human genome and play important roles in both physiology and disease. One important property of GPCRs is biased signaling, whereby ligand engagement selectively activates a subset of signaling pathways. There is great interest in the therapeutic development of biased ligands for GPCRs given that they have the potential to selectively target downstream signaling pathways of interest and treat diseases more safe and effective manner. However, the complexity of the structural and signaling properties of GPCRs has presented many challenges in developing biased ligands. Here, we introduce a novel and generalizable high-throughput screening approach for discovering biased ligands for GPCRs. Biased ligands can stabilize distinct receptor conformations, which directly affect receptor interaction with intracellular signaling proteins, resulting in different downstream signaling outcomes. Our method integrates high-throughput screening and statistical modeling to examine large mutant protein libraries and infer the ligand-receptor binding conformation based on mutation statistical patterns. The inferred binding conformations allow for efficient identification of candidate biased ligands based on their different binding interactions with the receptor. We applied our computer-aided high-throughput screening approach to search for biased ligands targeting the Complement 5a Receptor, an important GPCR involved in the immune response and cancer. Importantly, we identified a variety of biased mutants with distinct signaling properties. In the future, we aim to apply our platform to other GPCRs and promote the study and therapeutic application of GPCR biased signaling.
Download or read book Proceedings of the Practice and Experience in Advanced Research Computing 2017 on Sustainability Success and Impact written by David Hart and published by . This book was released on 2017-07-09 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Practice and Experience in Advanced Research Computing 2017 Jul 09, 2017-Jul 13, 2017 New Orleans, USA. You can view more information about this proceeding and all of ACM�s other published conference proceedings from the ACM Digital Library: http://www.acm.org/dl.
Download or read book Heterotrimeric G proteins written by Tim Gookin and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Heterotrimeric G-protein signaling is one of the most important mechanisms eukaryotic organisms use to sense their environment, and as such, it is one of the most studied molecular signaling systems in eukaryotic biology. In humans, the intracellular heterotrimeric G-protein complexes play critical roles in our sense of sight, taste, smell, emotion,and central physiology by receiving extracellular signals perceived and transduced by plasma-membrane localized seven transmembrane G-protein coupled receptors (GPCRs). These numerous and diverse physiological processes are facilitated by > 800 predicted and known GPCRs in humans which signal to a large number of G-protein compexes with a theoretical combinatorial complexity of over 900 configurations. Similar to metazoan organisms, plants also sense and respond to their environment and it is abundantly clear that plants propagate a numerous and diverse set of signals through the hetrotrimeric G-protein complex. But in plants the number of known G-protein complex subunits is greatly reduced. There are no confirmed GPCRs, and prior to finishing this dissertation, the number of Arabidopsis G-protein complex configurations was limited to three. The question remains as to how the relatively sparse repertoire of plant G-proteins can be responsible for the wide range of physiological processes affected by G-protein subunit mutation. In this work: 1) I detail the bioinformatic identification and empirical validation of new candidate GPCRs, 2) develop and improve the Bimolecular Fluorescence Complementation methodology for in-planta protein-protein interaction, 3) use this new methodology in conjunction with other experimental methods to show the actual number of plant G-protein subunits is greater than previously thought, and 4) characterize two homologous candidate GPCRs. While it appears certain the two proteins analyzed are not plant G[alpha]-coupling GPCRs, they do play critical role in maintaining metabolic homeostasis; double mutants exhibit developmental stage-specific catastrophic leaf death in response to short photoperiod.
Download or read book Deorphanising G Protein coupled Receptors written by Georgina Grace Joan Hazell and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: G protein coupled receptors (GPCRs) are the largest family of transmembrane receptors in the genome and are activated by a multitude of ligands including neuropeptides, hormones and sensory signals. The paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus are important mediators in homeostatic control. Many modulators of PVN/SON activity, including neurotransmitters and hormones act via GPCRs - in fact over 100 non-chemosensory GPCRs have been detected in either the PVN or SON. The introduction to this thesis begins with a comprehensive summary of GPCR expression within the PVN/SON, with a critique of the detection techniques used within the literature. Also discussed are some aspects of the regulation and known roles of GPCRs in the PVN/SON, as well the possible functional significance of orphan GPCRs. Particular interest is paid to the recently 'deorphanised' G protein-coupled oestrogen (E2) receptor, GPER, which is the first receptor to be acknowledged as a steroid binding GPCR (although there are conflicting studies regarding its affinity for E2) and is expressed in the PVN and SON. Steroids are known to have fast non-genomic effects that are thought to be mediated in-part by membrane-associated forms of the traditional steroid receptors (members of a family of transcription factors). However, the possible discovery of a fast E2 GPCR has raised speculation regarding the existence of other steroid binding GPCRs. Thus the experimental Chapters were undertaken to explore the concept of fast steroid receptors, with particular emphasis on their possible roles in neuroendocrine systems. Firstly, the distribution of the putative E2 receptor was investigated to give further insight into its possible in vivo roles. In the rodent, high levels of GPER gene and protein expression were detected in the oxytocin and vasopressin neurones in the PVN and SON, the anterior and intermediate lobe of the pituitary, adrenal medulla and renal medulla and pelvis, suggesting roles for GPER in multiple functions including hormone release. To clarify the controversy surrounding GPER as an E2 receptor, we investigated GPER function in vitro using a series of cell signalling assays. However, E2 did not stimulate GPER-mediated signalling, suggesting that either GPER remains an orphan GPCR, or the cell lines used in this study lacked a vital component for E2 activation of GPER. As the rapid effects of glucocorticoid have been reported in numerous brain regions (including the PVN and SON), endocrine, and other tissues, the second part of this thesis focussed on the search for a possible fast glucocorticoid receptor. We compared the tissue distribution gene expression profiles of approximately 125 orphan GPCRs common to human and rodent with tissues that are known to exhibit fast effects of steroids (e.g., hippocampus, PVN, SON, thymus, kidney, etc.). Of the 125 orphans,3 GPCRs (GPR108, GPR146, and TMEM87B) had distribution profiles that closely matched the regions/tissues of interest. These orphans were tested for glucocorticoid activation using a universal deorphanisation assay. However, the identity of the fast glucocorticoid receptor remains unknown, as none of the candidate orphan GPCRs responded to glucocorticoids.
Download or read book Molecular Modeling of Proteins written by Andreas Kukol and published by Humana Press. This book was released on 2017-04-30 with total page 474 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular Modeling of Proteins, Second Edition provides a theoretical background of various methods available and enables non-specialists to apply methods to their problems by including updated chapters and new material not covered in the first edition. This detailed volume opens by featuring classical and advanced simulation methods as well as methods to set-up complex systems such as lipid membranes and membrane proteins and continues with chapters devoted to the simulation and analysis of conformational changes of proteins, computational methods for protein structure prediction, usage of experimental data in combination with computational techniques, as well as protein-ligand interactions, which are relevant in the drug design process. Written for the highly successful Methods in Molecular Biology series, chapters include thorough introductions, step-by-step instructions and notes on troubleshooting and avoiding common pitfalls. Update-to-date and authoritative, Molecular Modeling of Proteins, Second Edition aims to aid researchers in the physical, chemical and biosciences interested in utilizing this powerful technology.
Download or read book Identifying Novel Protein Interactors of the Glucagon Superfamily of Receptors written by Gregory Gaisano and published by . This book was released on 2009 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt: G-protein coupled receptors (GPCRs) have been shown to act as part of GPCR associated protein complexes (GAPCs) which are required to appropriately transduce downstream signaling pathways leading to specific cellular actions. I hypothesize that there are distinct molecular effectors that couple to the glucagon superfamily of B-class GPCRs (glucagon, GLP-1, GLP-2, GIP receptors) to effect the myriad of reported actions in numerous target cells including regulation of insulin secretion, intestinal growth and appetite suppression. GLP-1R, GIPR, GLP-2R and GCGR were screened using a newly developed membrane-based split-ubiquitin yeast two-hybrid (MYTH) system to reveal 181 novel candidate protein interactors associated with signal transduction, transport, metabolism and cell survival. Each candidate was validated using yeast two-hybrid prey retransformation tests and by co-purification to confirm coupling to each receptors. The present work is the first demonstration of a split-ubiquitin interaction screen using in situ membrane expressed GPCRs of the secretin-like B class.
Download or read book Identification and Characterization of G protein Coupled Receptors Expressed Preferentially in Pancreatic beta Cells written by Nir E. Rubins and published by . This book was released on 2004 with total page 76 pages. Available in PDF, EPUB and Kindle. Book excerpt:
