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

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.

G-Protein Coupled Receptors (GPCRs) are not only the largest protein family in the human genome but are also the single biggest target for therapeutic agents. Research into GPCRs is therefore growing at a fast pace and the range of techniques that can be applied to GPCRs is vast and continues to grow. This book provides an invaluable bench-side guide into the best and most up-to-date techniques for current and future research on GPCRs. With contributions from leading international authorities, this book equips readers with clear and detailed protocols for both well-known and up-and-coming techniques along with hints and tips for success. All the methods have been tried and tested by leading international research labs and are presented in easy-to-follow stages along with a useful overview of each technique. This book is an essential resource for all researchers in molecular biology, biochemistry, pharmacology and for graduate students.

Covering recently developed methods in membrane-bound receptors, this book emphasizes receptor structure and function, knowledge of which is essential to the study of signal transduction. G Protein-Coupled Receptors has culled contributors from domestic and international sources, providing a broad base of knowledge. Some topics covered are the r

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) 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.

G Protein-Coupled Receptors, Part B, Volume 195 represents the largest class of cell H103 surface proteins that have intricate involvement in nearly every physiological process in our body. Approximately one third of the clinically prescribed medicines target GPCRs and the quest to improve the exiting GPCR-targeting therapeutics continues. Sections in this volume include Adhesion G protein-coupled receptors: Structure and functions, Molecular and cellular mechanisms underlying brain region-specific cannabinoid receptor modulation by estradiol across the rodent estrus cycle, Probing the orphan receptors: Tools and directions, Asymmetric activation of Class C GPCRs, Common and selective signal transduction mechanisms of GPCRs, and much more. Covers a broad range of topics related to GPCR activation and signaling Provides several receptor systems, with an emphasis on emerging paradigms Includes different processes and model systems, with a focus on GPCRs

G Protein-Coupled Receptors, Part A, Volume 193 in the Progress in Molecular Biology and Translational Science series, highlights new advances in the field. G protein-coupled receptors (GPCRs) represent the largest class of cell surface proteins with an intricate involvement of nearly every physiological process in our body. Approximately, one third of the clinically prescribed medicines target GPCRs and the quest to improve the exiting GPCR-targeting therapeutics continues. These two volumes are focused on activation, signaling and regulation of GPCRs with specific examples of receptor systems and cellular processes. - Covers a broad range of topics related to GPCR activation and signaling - Covers several receptor systems with an emphasis on emerging paradigms - Covers different processes and model systems with a focus on GPCRs

Allosteric Modulation of G Protein-Coupled Receptors reviews fundamental information on G protein-coupled receptors (GPCRs) and allosteric modulation, presenting original research in the area and collectively providing a comprehensive description of key issues in GPCR allosteric modulation. The book provides background on core concepts of molecular pharmacology while also introducing the most important advances and studies in the area. It also discusses key methodologies. This is an essential book for researchers and advanced students engaged in pharmacology, toxicology and pharmaceutical sciences training and research. Many of the GPCR-targeted drugs released in the past decade have specifically worked via allosteric mechanisms. Unlike direct orthosteric-acting compounds that occupy a similar receptor site to that of endogenous ligands, allosteric modulators alter GPCR-dependent signaling at a site apart from the endogenous ligand. Recent methodological and analytical advances have greatly improved our ability to understand the signaling mechanisms of GPCRs. We now know that allostery is a common regulatory mechanism for all GPCRs and not – as we once believed – unique to a few receptor subfamilies. - Introduces background on core concepts of molecular pharmacology, including statistical analyses, non-linear regression, complex models and GPCR-dependent signal transduction as they relate to allosteric modulation - Discusses critical advances and landmark studies, including discoveries in the area of GPCR allosteric modulation, which are reviewed for their importance in positive and negative regulation, protein-protein interactions, and small molecule drug discovery - Includes key methodologies used to study allosteric modulation at the in silico, in vitro, and in vivo levels of drug discovery and characterization

G protein-coupled receptors (GPCRs) are one of the most important target classes in pharmacology and are the target of many blockbuster drugs. Yet only with the recent elucidation of the rhodopsin structure have these receptors become amenable to a rational drug design. Based on recent examples from academia and the pharmaceutical industry, this book demonstrates how to apply the whole range of bioinformatics, chemoinformatics and molecular modeling tools to the rational design of novel drugs targeting GPCRs. Essential reading for medicinal chemists and drug designers working with this largest class of drug targets in the human genome.