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This book summarizes the progress made to functional immobilize G protein-coupled receptors (GPCRs) through site-specific or orientated recognition in both non-covalent and covalent manners. The last decade is the dawn of the “post-structural biology” era for G protein-coupled receptor research. As an emerging approach for state-of-the-art immobilization, this book discusses efforts to explore the elegance of naturally-occurring biochemical reactions by using their high specificity and robust reactivity in the complex system, such as site-specific conjugation by covalent recognition between enzymes and their substrates. With the perspective of protein-drug interactions, this book also reviews the applications of protein immobilization, with an emphasis on G protein-coupled receptors, in drug discovery and protein-ligand interaction analysis. In addition, the merits, opportunities and disadvantages are analyzed for different immobilization methods, and a perspective for future directions is presented. Given its scope, this book appeals to a broad readership, particularly researchers engaged in the field of analytical chemistry, bioconjugate chemistry, and chemical biology, and other related field, as well as teachers of relevant majors in colleges and universities.

GPCRS: Structure, Function, and Drug Discovery provides a comprehensive overview of recent discoveries and our current understanding of GPCR structure, signaling, physiology, pharmacology and methods of study. In addition to the fundamental aspects of GPCR function and dynamics, international experts discuss crystal structures, GPCR complexes with partner proteins, GPCR allosteric modulation, biased signaling through protein partners, deorphanization of GPCRs, and novel GPCR-targeting ligands that could lead to the development of new therapeutics against human diseases. GPCR association with, and possible therapeutic pathways for, retinal degenerative diseases, Alzheimer's disease, Parkinson's disease, cancer and diabetic nephropathy, among other illnesses, are examined in-depth. - Addresses our current understanding and novel advances in the GPCR field, directing readers towards recent finding of key significance for translational medicine - Combines a thorough discussion of structure and function of GPCRs with disease association and drug discovery - Features chapter contributions from international experts in GPCR structure, signaling, physiology and pharmacology

Oligomerization in Health and Disease: From Enzymes to G Protein-Coupled Receptors, Volume 169 in the Progress in Molecular Biology and Translational Science series, provides in-depth reviews on topics of exceptional scienti?c importance. Topics of note in this new release include Computational prediction and re-design of aberrant oligomerization, Oligomerization of G protein-coupled receptors: an historical overview, Prediction and targeting of GPCR oligomer interfaces, GPCR Oligomerization dynamics: Functional consequences, GPCR heteromerization in neuropsychiatric disorders, Structural basis of regulation and oligomerization of human cystathionine ß-synthase, and Oligomerization of Porphobilinogen Synthase. - Includes comprehensive coverage of molecular biology - Presents ample use of tables, diagrams, schemata and color figures to enhance the reader's ability to rapidly grasp the information provided - Contains contributions from renowned experts in the field of molecular biology

From Structure to Clinical Development: Allosteric Modulation of G Protein-Coupled Receptors, Volume 88, the latest release in the Advances in Pharmacology series, presents a variety of chapters from the best authors in the field. Chapters in this updated edition include Targeting muscarinic M1 receptor in neurodegeneration, Photo-switchable allosteric ligands, Computational approaches for the design of mGlu receptor allosteric modulators, Allosteric modulation of GLP-1 receptor in metabolic disorders, Group II mGluR roles in the nervous system and their roles in addiction, RAMPs as allosteric modulators of Class B GPCRs, Structure-based discovery and development of mGlu5 NAMs, and much more. - Includes the authority and expertise of leading contributors in pharmacology - Presents the latest release in the Advances in Pharmacology series

G Protein Signaling Pathways in Health and Disease, Volume 161 in the Progress in Molecular Biology and Translational Science series, provides informative and exciting monographs on a wide variety of research topics related to G Protein Signaling Pathways in Health and Disease. The series gives in-depth knowledge on the important molecular biological aspects of organismal physiology and function, along with insights on how this knowledge can be applied to understand and ameliorate human disease. This updated release covers Diseases associated with mutations in CNGA3, Mutations in arrestins, Diseases caused by mutations in GPR101, Diseases caused by mutations in lutropin receptor, and much more. - Comprises 15-20 chapters, providing substantial coverage on a given topic - Contains ample use of tables, diagrams, schemata and color figures to enhance the reader's ability to rapidly grasp the information provided in each chapter - Provides a comprehensive guide to the latest information available on prions, viruses, bacteria, and eukaryotes

G-Protein-Coupled Receptors, Part B, 2nd Edition, Volume 149, the latest release in the Methods in Cell Biology series, continues the legacy of this premier serial with quality chapters authored by leaders in the field. This volume covers Optical Approaches for Visualization of Arrestin Binding to Muscarinic Receptors, Luciferase Reporter Assay for Unlocking Ligand-mediated Signaling of GPCRs, Assays to Measure GPCR Dependent Cellular Migration, Characterization of the Frizzled GPCRs, Binding Assays for Bradykinin and Angiotensin Receptors, Detection of Misfolded Rhodopsin Aggregates in Cells, Measuring GPCR Ubiquitination and Trafficking, Culture of Primary Neurons and its Use in Studying GPCR Trafficking, and much more. - Covers the increasingly appreciated cell biology field of G-protein-coupled receptors - Includes both established and new technologies - Contributed by experts in the field

This book will provide current understandings about two ubiquitously expressed metabotropic GPCRs, G-coupled purinoreceptor type 2 (P2Y) and Takeda G-protein-coupled bile acid receptor 5 (TGR5). G protein coupled receptors (GPCRs) are the largest family of proteins implicated in majority of cellular responses. The two receptor sub-families play a central role in many physiological functions as well as in many pathological conditions. This book offers up-to-date information on the physiological functions, signaling pathways and regulatory mechanisms of P2Y and TGR5 receptors. In addition, this book provides a comprehensive overview about the abnormalities of P2Y/TGR5 receptors and their contribution in the development and progression of pathological conditions. It also covers the currently available natural, chemical and pharmacological agents targeting these two receptor families and their therapeutic implications in P2Y and TGR5 associated disorders. This book is a valuable sourcefor beginners and researchers to follow the rapidly progressing field of these two GPCR subfamily members.

International Review of Cell and Molecular Biology reviews and details current advances in cell and molecular biology. The IRCMB series has a worldwide readership, maintaining a high standard by publishing invited articles on important and timely topics that are authored by prominent cell and molecular biologists. The articles published in IRCMB have a high impact and an average cited half-life of 9 years. This great resource ranks high amongst scientific journals dealing with cell biology. - Publishes only invited review articles on selected topics - Authored by established and active cell and molecular biologists, and drawn from international sources - Offers a wide range of perspectives on specific subjects

G Protein-Coupled Receptors: Emerging Paradigms in Activation, Signaling and Regulation, Part A, Volume 337 in the International Review of Cell and Molecular Biology series, reviews and details current advances in cell and molecular biology. The IRCMB series has a worldwide readership, maintaining a high standard by publishing invited articles on important and timely topics that are authored by prominent cell and molecular biologists. This new release includes comprehensive sections on the classical paradigms of GCPR signaling and regulation, the family of small GTPases: Beyond heterotrimeric G proteins, GPCR endocytosis: Arrestins, arrestin-like proteins, signaling from internalized G Protein-Coupled Receptors, GPCR kinases, and more. - Publishes only invited review articles on selected topics - Authored by established and active cell and molecular biologists whose work is drawn from international sources - Offers a wide range of perspectives on specific subjects

G Protein-Coupled Receptors in Immune Response and Regulation, Volume 136 presents emerging concepts related to the role of GPCRs in immune response and regulation. Users will find updated chapters on a variety of topics, including Beta-adrenergic signaling in the onset and progression of asthma, the Emerging roles of Regulators of G protein signaling (RGS) proteins in the immune system, information on Kinin receptors in immune response and pathogenic infections, and sections on GPCR signaling in C. elegans and its implications in immune response, GPCR Kinases in Inflammatory response and signaling, and GRK2 in Inflammation: Regulation of T cell receptors and IgE signaling. Chapters in this book discuss not only the well-known aspects of GPCR signaling in immunology, but also presents many emerging paradigms that have not yet been reported in classical textbooks. Each chapter presents a forward-looking discussion, providing a glimpse of the tremendous potential associated with the specific receptor systems discussed. - Brings together contributions from leading experts in the area of GPCR biology - Discusses current paradigms and the future potential of understanding GPCR signaling in immune response and regulation - Presents the first of its kind book to focus on specific GPCR systems in various aspects of immunology, all brought together in one volume

G-protein-coupled receptors (GPCRs) are believed to be the largest family of membrane proteins involved in signal transduction and cellular responses. They dimerize (form a pair of macromolecules) with a wide variety of other receptors. The proposed book will provide a comprehensive overview of GPCR dimers, starting with a historical perspective and including, basic information about the different dimers, how they synthesize, their signaling properties, and the many diverse physiological processes in which they are involved. In addition to presenting information about healthy GPCR dimer activity, the book will also include a section on their pathology and therapeutic potentials.

G-Protein-Coupled Receptors: Signaling, Trafficking, and Regulation, a new volume in the Methods in Cell Biology series continues the legacy of this premier serial with quality chapters authored by leaders in the field. This volume covers research methods in G-Protein-Coupled Receptors, and includes sections on such topics signaling, trafficking and regulation. - Covers the increasingly appreciated cell biology field of G-protein-coupled receptors - Includes both established and new technologies - Contributed by experts in the field - Covers topics such as signaling, trafficking, and regulation

Latest research on Adhesion GPCRs has unearthed surprising revelations about the events that govern the signal transduction of these receptor molecules and the cellular and organ requirements for these signals. Unexpected and unprecedented findings suggest that Adhesion GPCRs constitute a group of receptors that sense mechanical stimuli and transcode them into metabotropic signals through the action of a novel activation paradigm. Interdisciplinary efforts transcending many areas of biomedical research including pharmacology, physiology, genetics, cell biology, structural biology, biochemistry and bioinformatics were necessary to unveil these fundamental properties. The scientific leaders in the field that carried this research effort have teamed up here to provide a comprehensive overview of our current understanding, how Adhesion GPCRs signal and how these receptors shape organ structure and function.

G protein-coupled receptors (GPCRs) constitute the largest superfamily of cell surface receptors that regulate a variety of cell functions. Over the past few decades great progress has been made in defining the roles of intracellular trafficking in controlling the functionality of the receptors as well as in the development of various human diseases. This volume of Progress in Molecular Biology and Translational Science reviews the recent understanding of GPCR trafficking regulators and molecular mechanisms. - Written by future leaders in the pain field - Covers a wide range of targets - Contains provocative ideas about GPCR trafficking

G protein-coupled receptors (GPCRs) are heptahelical transmembrane receptors that convert extra-cellular stimuli into intra-cellular signaling, and ultimately into biological responses. Since GPCRs are natural targets for approximately 40% of all modern medicines, it is not surprising that they have been the subject of intense research. Notwithstanding the amount of data generated over the years, discovering ligands of these receptors with optimal therapeutic properties is not straightforward and has certainly been hampered for years by the lack of high-resolution structural information about these receptors. Luckily, there has been a steady increase of high-resolution crystal structures of these receptors since 2007, and this information, integrated with dynamic inferences from computational and experimental methods, holds great potential for the discovery of new, improved drugs. This book, which provides, for the first time, state-of-the-art views on modeling and simulation of GPCRs, is divided into 4 parts. In the first part, the impact of currently available GPCR crystal structures on structural modeling is discussed extensively as are critical insights from simulations in the second part of the book. The third part reports recent progress in rational ligand discovery and mathematical modeling, whereas the fourth part provides an overview of bioinformatics tools and resources that are available for GPCRs.

In this thematic volume of Progress in Molecular Biology and Translational Science, researchers reflect on recent developments and research surrounding G protein-coupled receptors. The chapters cover a large breadth of research, including GPCR role in stem cell function and pharmacology. Authors explore in-depth research techniques and applications of GPCR usage, covering theory, laboratory approaches, and unique qualities that make GPCRs a crucial tool in microbiological and cancer research. - Contributions from leading authorities - Informs and updates on all the latest developments in the field

This new volume of Methods in Enzymology continues the legacy of this premier serial with quality chapters authored by leaders in the field. This volume covers G protein coupled receptors, and includes chapters on such topics as GPCR modelling, interactions with other molecules, virtual screening and GPCR activation. - Continues the legacy of this premier serial with quality chapters authored by leaders in the field - Covers G protein coupled receptors - Contains chapters on such topics as GPCR modelling, interactions with other molecules, virtual screening and GPCR activation

Obesity is an epidemic with enormous health, economic and social burdens. Current drugs for obesity treatment are far from ideal in terms of efficacy and side effects. Reviews in this volume of Progress in Molecular Biology and Translational Science summarize current status in studies of a number of G protein-coupled receptors that were shown to be promising targets for obesity treatments. Some of these receptors also cause monogenic obesity in humans. - Subject matter: obesity is an epidemic and G protein-coupled receptors are promising drug targets, with significant potential as new anti-obesity drugs - Chapters are written by leading experts

This new volume of Methods in Enzymology continues the legacy of this premier serial by containing quality chapters authored by leaders in the field. This volume covers G protein coupled receptors and includes chapters on such topics as G protein-coupled receptor trafficking motifs, structure-based virtual screening, and automation-friendly high throughput assays for identification of pharmacoperone drugs. - Continues the legacy of this premier serial with quality chapters authored by leaders in the field - Covers G protein coupled receptors - Contains chapters on such topics as G protein-coupled receptor trafficking motifs, structure-based virtual screening, and automation-friendly high-throughput assays for identifying pharmacoperone drugs

This new volume of Methods in Enzymology continues the legacy of this premier serial by containing quality chapters authored by leaders in the field. This volume covers G protein coupled receptors and includes chapters on such topics as post-translation modification of GPCR in relationship to biased agonism, structure-based virtual screening, and GPCR oligomerization in the brain. - Continues the legacy of this premier serial with quality chapters authored by leaders in the field - Covers G protein coupled receptors - Contains chapters on such topics as post-translation modification of GPCR in relationship to biased agonism, structure-based virtual screening, and GPCR oligomerization in the brain

LESLIE L. IVERSEN The present series of volumes is well timed, as the impact of molecular genetics on pharmacology has been profound, and a comprehensive review of the rapid advances of the past decade is much needed. Since the pioneering work of Dale, Ariens, and others in the early years of this century, much of pharmacology has been founded on the concept of receptors. To begin with, the receptor was conceived of as a'black box,'which recognized and transduced the biological effects of neurotransmit­ ters, hormones, or other biological messengers-and which could also represent a target for man-made drugs. It is only in the last two decades that'molecular pharmacology'has blossomed, first with the advent of radioligand binding techniques and second messenger studies which greatly facilitated the biochemical study of drug-receptor interactions, and latterly with increasing knowledge of the molecular architecture of the receptor proteins themselves. This started with the traditional biochemical approach of isolating and purifying the receptor molecules. This proved to be a task of immense technical difficulty because of the low density of receptors in most biological source tissues, although there were some notable successes, e. g., the purification of the nicotinic acetylcholine receptor from the electric organ of Torpedo. It was the ap­ plication of molecular genetics technology during the 1980s, however, which really accelerated progress in this field.

Among the many GPCRs discovered, the calcitonin family of receptors comprise of members that regulate a number of physiological processes and are involved in many pathological conditions. Therefore, understanding how these receptors function is a critical question in the field. When Foord and his colleagues discovered that a single transmembrane protein called Receptor Activity Modifying Proteins (RAMPs) could modulate the surface expression of GPCRs of the calcitonin family, it widely opened the field of receptor life cycle. Hundreds of studies have confirmed the importance of RAMPs in the life cycle of this receptor family. Receptor biology is a rapidly expanding field and with the advances in cell and molecular biology and in vivo techniques, it is very likely that the field of RAMPs will explode further and many unanswered questions will be answered with in the next few years.

Main Question: G protein coupled receptors are involved in highly efficient and specific activation of signalling pathways. How do GPCR signalling complexes get assembled to generate such specificity? In order to answer this question, we need to understand how receptors and their signalling partners are synthesized, folded and quality-controlled in order to generate functional proteins. Then, we need to understand how each partner of the signalling complex is selected to join a complex, and what makes this assembly possible. GPCRs are known to be able to function as oligomers, what drives the assembly into oligomers and what will be the effects of such organization on specificity and efficacy of signal transduction. Once the receptor complexes are assembled, they need to reach different locations in the cell; what drives and controls the trafficking of GPCR signalling complexes. Finally, defects in synthesis, maturation or trafficking can alter functionality of GPCRs signalling complexes; how can we manipulate the system to make it function normally again? Pharmacological chaperones may just be part of the answer to this question.

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.

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

G protein-coupled receptors (GPCRs) transduce signals from a diverse array of endogenous ligands, including ions, amino acids, nucleotides, lipids, peptides, and large glycoprotein hormones. They are also responsible for our sensing of exogenous stimuli, including photons and odorants. GPCRs regulate almost every aspect of our physiological functions. It is estimated that 40% to 50% of currently used therapeutic drugs target GPCRs directly or indirectly. Because the current drugs target only a small portion of the GPCRs, opportunities for targeting the remaining GPCRs is enormous. This volume reviews the latest developments in this rapidly advancing field. - This series provides a forum for discussion of new discoveries, approaches, and ideas - Contributions from leading scholars and industry experts - Reference guide for researchers involved in molecular biology and related fields

G protein-coupled receptors (GPCRs) transduce signals from a diverse array of endogenous ligands, including ions, amino acids, nucleotides, lipids, peptides, and large glycoprotein hormones. They are also responsible for our sensing of exogenous stimuli, including photons and odorants. GPCRs regulate almost every aspect of our physiological functions. It is estimated that 40% to 50% of currently used therapeutic drugs target GPCRs directly or indirectly. Because the current drugs target only a small portion of the GPCRs, opportunities for targeting the remaining GPCRs is enormous. This volume reviews the latest developments in this rapidly advancing field. - This series provides a forum for discussion of new discoveries, approaches, and ideas - Contributions from leading scholars and industry experts - Reference guide for researchers involved in molecular biology and related fields

Based on the international workshop GPCRs: From Deorphanisation to Lead Structure Identification, held in Berlin in May 2006, the book highlights the following topics: Structure of GPCRs, Design of GPCR Ligands, GPCR Signalling, Deorphanization and Assay Development. All chapters are written by leading experts in the field, discussing the most recent state of the art. They give insight into the approaches taken by industry and academia to address GPCRs and depict how mature this target class-oriented research has become in the last decade. The book reflects the actual trends in the fast-emerging field of GPCR research in academia and industry.

G protein-coupled receptors (GPCRs) are membrane proteins that transduce a vast array of extracellular signals into intracellular reactions ranging from cell-cell communication processes to physiological responses. They play an important role in a variety of diseases from cancer and diabetes, to neurodegenerative, inflammatory and respiratory disorders. GPCRs are therefore of utmost interest in drug development: over half of all prescription drugs currently on the market act by targeting these receptors directly or indirectly. G Protein-coupled Receptors: Molecular Pharmacology provides a clear summary of the current knowledge in this fast-evolving field. The book sets out with an introduction to signalling molecules and their receptors, and an overview of the technical approaches used to investigate these interactions. Structural, functional and especially pharmacological aspects of GPCRs are then discussed in more detail and much attention is devoted to the analysis and interpretation of experimental data. The now widespread use of recombinant cell lies, receptor mutants and related artifices in drug research is critically evaluated. Special attention is also devoted to topical but often poorly understood concepts, such as insurmountable antagonism, inverse agonism and allosteric interactions. By combining general information with the major state-of-the-art concepts in GPCR-research, this outstanding book equips the reader with the necessary background for understanding and critically evaluating the current literature. Written by two experts from academia and industry, G Protein-coupled Receptors: Molecular Pharmacology offers a unique view of academic and applied approaches aiming to reveal new ideas in pharmaceutical research. The book is of interest to anyone involved in drug development and preclinical research and those who need to function within multi-disciplinary teams in the pharmaceutical industry: from investigators to product managers or clinicians who seek to have a broad mechanistic understanding of drug-receptor interactions. It is also an invaluable resource for final year undergraduate and postgraduate students in pharmacology and cell and molecular biology.

This book provides a broad base of knowledge of G-protein-coupled receptors. Useful at both the university and industrial levels, this book is of particular interest to those who are developing therapeutic approaches to diseases using drugs that influence receptor activation.

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

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.