Table of Contents

Introduction, K.H. Lundstrom and M.L. Chiu

Biology of G Protein-Coupled Receptors, K. Lundstrom

Introduction
Families of GPCRs
Coupling to G Proteins
GPCR Desensitization
Other Signaling Pathways
Trafficking of GPCRs
Resensitization
Conclusions
G Protein Coupled Receptors as Targets for Drug Discovery, T. Esbenshade
Introduction
GPCR Family Overview
GPCR Tractability: Current Therapeutics
GPCR Drug Discovery
Novel GPCR Features and Impact on Drug Discovery Approaches
Conclusions
G Protein-Coupled Receptors as Cardiovascular Drug Targets, M. Scheinin and A. Snapir
Cardiovascular Physiology, Pharmacology, and Therapeutics
Drugs in Development and Novel Drugs Targets
Receptor Subtypes as Novel Targets
Receptor Gene Polymorphisms
Concluding Remarks
G Protein-Coupled Receptors and Cancer, M.J. Smit and R.A. Bakker
Introduction
Family A GPCRs
Family C GPCRs
Frizzled/Smoothened Family of GPCRs
Virally Encoded GPCRs
Orphan GPCRs
Conclusions
G Protein-Coupled Receptors in Metabolic Disease, R.M. Reilly and C.A. Collins
Introduction
Central Mediation of Feeding and Energy Homeostasis
Peripheral Signals Affecting Nutrient Sensing and Utilization
Conclusions
G Protein-Coupled Receptors in CNS Drug Discovery, R. Raddatz and D.S. Hartman
Introduction
Psychiatric Diseases
Pain and Analgesia
Neurodegeneration
Neuroendocrine Function
Orphan GPCRs in the CNS
Conclusions
Recombinant G Protein-Coupled Receptors for Drug Discovery, K. Lundstrom
Introduction
Cell-Free Translation
E. coli Expression
Other Prokaryotic Systems
Yeast Expression
Insect Cells
Mammalian Expression
Comparison of Expression Systems
Conclusions
High Throughput Screening Assays for G Protein-Coupled Receptors, U. Warrior, S. Gopalakrishnan, J. Vanhauwe, and D. Burns
Introduction
Source of Material and Assay Diversity
High Throughput Screening
Receptor Binding Assays—General Considerations
Functional GPCR Assays
Inverse Agonists and Constitutive Activities
Microphysiometer Assays
Screening for Modulators of Orphan Receptors
Conclusions
Molecular Bioinformatics of Receptor Binding and Activation, K.P. Willey, H. Obermann, and J.B. Procter
Not All 7TM Receptors are GPCRs
Receptor Classification by Ligand Size
Ligand Diversity Conforms to Receptor Phylogeny
Structural Flexibilities of Membrane Receptors
Molecular Bioinformatics in Drug Discovery
Sequence and Structural Searches for an Activation Mechanism
The Cysteine Shuffle
Redox Control of Receptor Activation
Smells Rank as the Smallest 7TMR Agonists
Bioinformatics with Biological Sense
Structure and Dynamics of G Protein-Coupled Receptors, J. Klein-Seetharaman and M.C. Loewen
Introduction
Structure, Stability, Dynamics, and Conformational Changes of Rhodopsin
Structures, Dynamics, and Conformational Changes of GPCRs
Conclusions
Towards Crystallization of G Protein-Coupled Receptors, M.L. Chiu and M.P. MacWilliams
Introduction
Overexpression and Purification
Detergent Selection
Sample Preparation
Crystallization Methods
Micelles and Bicelles
Lipidic Mesophases
Bicelles, Lipopeptides, and Nanodiscs
Crystallization
Case Study: Rhodopsin
Conclusions
Novel Solid-State NMR Methods for Structural Studies on G Protein-Coupled Receptors, A. Lange and M. Baldus
Introduction
High-Resolution Solid State NMR
Sample Preparation
Applications
Conclusions and Outlook
Structural Genomics Initiatives, K. Lundstrom
Introduction
Structural Genomics Programs on Membrane Proteins
Structural Genomics Initiatives Including GPCRs
MePNet Approach
Conclusions
Molecular Basis of Dimerization of Family A G Protein-Coupled Receptors, G. Milligan
Introduction
Quarternary Structure of Family A GPCRs
Consequences of the Dimerization of the Family A GPCRs
The Mechanisms of Dimerization of the Family A GPCRs
Conclusions
Orphan Receptors: Promising Targets for Drug Discovery, Y. Saito, Z. Wang, and O. Civelli
Introduction
Search for Endogenous Ligands of Orphan GPCRs
Example of Deorphanization: The MCH Systems and Its Impact on Drug Discovery
Conclusions and Perspectives
Index