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Author: Christopher B. Roth Publisher: ISBN: Category : Beta adrenoceptors Languages : en Pages : 204
Book Description
G-protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors, accounting for >1% of the human genome and are the target of more than 30% of currently marketed pharmaceuticals. Although structural information is vital to the thorough understanding of this important class of receptors, progress has been greatly limited by the instability of these molecules in the detergent solutions used for their extraction, purification, and crystallization. To surmount this obstacle, we developed an engineering strategy where targeted amino acid substitutions were introduced at transmembrane helix (TM) interfaces in order to stabilize the receptor core fold, while at the same time maintaining normal receptor biochemistry. In the first chapter, background information on GPCR phylogeny, structure, and mechanism is reviewed. In the second chapter, the development of technology and methods for characterizing engineered [beta]-adrenergic receptors is described, including a high throughput flow-cytometric determination of receptor expression, and a novel HPLC-based system for rapid screening of receptor aggregation state and thermal stability. In the third chapter, the discovery of a stabilized mutant of the [beta]2-adrenergic receptor ([beta]2AR) is described where mutation of Glu-1223·41 to tryptophan resulted in a dramatic increase in receptor thermal stability while preserving near wild-type biochemistry and may do so by stabilizing the conserved break in TM5 at Pro-2115·50 . In the final chapter, agonist docking studies were performed using the recently published [beta]2AR X-ray crystal structure, which revealed that flexibility in TM5 is critical to the full engagement of key agonist-binding residues in TM3, TM5, TM6 and TM7, and may be an early step in the GPCR activation mechanism.
Author: Publisher: ScholarlyEditions ISBN: 1481641980 Category : Science Languages : en Pages : 22
Book Description
beta Adrenergic Receptors—Advances in Research and Application: 2012 Edition is a ScholarlyPaper™ that delivers timely, authoritative, and intensively focused information about beta Adrenergic Receptors in a compact format. The editors have built beta Adrenergic Receptors—Advances in Research and Application: 2012 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about beta Adrenergic Receptors in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of beta Adrenergic Receptors—Advances in Research and Application: 2012 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.
Author: Guillaume Lebon Publisher: Springer ISBN: 3030245918 Category : Science Languages : en Pages : 299
Book Description
This book introduces readers to the latest advances in G protein-coupled receptor (GPCR) biology. It reviews our current understanding of the structural basis of ligand binding and allosteric mechanisms, following a decade of technological breakthroughs. Several examples of structure-based drug discovery are presented, together with the future challenges involved in designing better drugs that target GPCRs. In turn, the book illustrates the important concept of GPCR biased signaling in physiological contexts, and presents fluorescent- and light-based methodologies frequently used to measure GPCR signaling or to trace their dynamics in cells upon ligand activation. Taken together, the chapters provide an essential overview and toolkit for new scientific investigators who plan to develop GPCR projects. All chapters were written by experts in their respective fields, and share valuable insights and powerful methodologies for the GPCR field.
Author: Publisher: ScholarlyEditions ISBN: 1481617087 Category : Medical Languages : en Pages : 49
Book Description
Adrenergic beta Receptors—Advances in Research and Application: 2012 Edition is a ScholarlyBrief™ that delivers timely, authoritative, comprehensive, and specialized information about Adrenergic beta Receptors in a concise format. The editors have built Adrenergic beta Receptors—Advances in Research and Application: 2012 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Adrenergic beta Receptors in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Adrenergic beta Receptors—Advances in Research and Application: 2012 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.
Author: Publisher: Academic Press ISBN: 0123849225 Category : Science Languages : en Pages : 257
Book Description
This volume of Current Topics in Membranes focuses on adrenergic receptor biology, beginning with a review of past successes and historical perspectives then further discussing current general trends in adrenic receptor studies in various contexts. This publication also includes discussions of the role and relationship of adrenergic receptors to different systems and diseases, establishing adrenergic receptor biology as a needed, practical reference for researchers.
Author: Adriano D. Andricopulo Publisher: Frontiers Media SA ISBN: 2889457443 Category : Languages : en Pages : 415
Book Description
Chemoinformatics is paramount to current drug discovery. Structure- and ligand-based drug design strategies have been used to uncover hidden patterns in large amounts of data, and to disclose the molecular aspects underlying ligand-receptor interactions. This Research Topic aims to share with a broad audience the most recent trends in the use of chemoinformatics in drug design. To that end, experts in all areas of drug discovery have made their knowledge available through a series of articles that report state-of-the-art approaches. Readers are provided with outstanding contributions focusing on a wide variety of topics which will be of great value to those interested in the many different and exciting facets of drug design.
Author: Christian Holm Publisher: Springer Science & Business Media ISBN: 3540877053 Category : Technology & Engineering Languages : en Pages : 248
Book Description
“Soft matter” is nowadays used to describe an increasingly important class of - terials that encompasses polymers, liquid crystals, molecular assemblies building hierarchical structures, organic-inorganic hybrids, and the whole area of colloidal science. Common to all is that ?uctuations, and thus the thermal energy k T and B entropy, play an important role. “Soft” then means that these materials are in a state of matter that is neither a simple liquid nor a hard solid of the type studied in hard condensed matter, hence sometimes many types of soft matter are also named “c- plex ?uids. ” Soft matter, either of synthetic or biological origin, has been a subject of physical and chemical research since the early ?nding of Staudinger that long chain mo- cules exist. From then on, synthetic chemistry as well as physical characterization underwent an enormous development. One of the outcomes is the abundant pr- ence of polymeric materials in our everyday life. Nowadays, methods developed for synthetic polymers are being more and more applied to biological soft matter. The link between modern biophysics and soft matter physics is quite close in many respects. This also means that the focus of research has moved from simple - mopolymers to more complex structures, such as branched objects, heteropolymers (random copolymers, proteins), polyelectrolytes, amphiphiles and so on.
Author: Jean-Paul Renaud Publisher: John Wiley & Sons ISBN: 1118900502 Category : Medical Languages : en Pages : 1367
Book Description
With the most comprehensive and up-to-date overview of structure-based drug discovery covering both experimental and computational approaches, Structural Biology in Drug Discovery: Methods, Techniques, and Practices describes principles, methods, applications, and emerging paradigms of structural biology as a tool for more efficient drug development. Coverage includes successful examples, academic and industry insights, novel concepts, and advances in a rapidly evolving field. The combined chapters, by authors writing from the frontlines of structural biology and drug discovery, give readers a valuable reference and resource that: Presents the benefits, limitations, and potentiality of major techniques in the field such as X-ray crystallography, NMR, neutron crystallography, cryo-EM, mass spectrometry and other biophysical techniques, and computational structural biology Includes detailed chapters on druggability, allostery, complementary use of thermodynamic and kinetic information, and powerful approaches such as structural chemogenomics and fragment-based drug design Emphasizes the need for the in-depth biophysical characterization of protein targets as well as of therapeutic proteins, and for a thorough quality assessment of experimental structures Illustrates advances in the field of established therapeutic targets like kinases, serine proteinases, GPCRs, and epigenetic proteins, and of more challenging ones like protein-protein interactions and intrinsically disordered proteins
Author: Sun Hongmao Publisher: Woodhead Publishing ISBN: 0081001053 Category : Medical Languages : en Pages : 293
Book Description
This book is not going to be an exhaustive survey covering all aspects of rational drug design. Instead, it is going to provide critical know-how through real-world examples. Relevant case studies will be presented and analyzed to illustrate the following: how to optimize a lead compound whether one has high or low levels of structural information; how to derive hits from competitors' active compounds or from natural ligands of the targets; how to springboard from competitors' SAR knowledge in lead optimization; how to design a ligand to interfere with protein-protein interactions by correctly examining the PPI interface; how to circumvent IP blockage using data mining; how to construct and fully utilize a knowledge-based molecular descriptor system; how to build a reliable QSAR model by focusing on data quality and proper selection of molecular descriptors and statistical approaches. A Practical Guide to Rational Drug Design focuses on computational drug design, with only basic coverage of biology and chemistry issues, such as assay design, target validation and synthetic routes. - Discusses various tactics applicable to daily drug design - Readers can download the materials used in the book, including structures, scripts, raw data, protocols, and codes, making this book suitable resource for short courses or workshops - Offers a unique viewpoint on drug discovery research due to the author's cross-discipline education background - Explores the author's rich experiences in both pharmaceutical and academic settings
Author: Publisher: Academic Press ISBN: 0080961592 Category : Science Languages : en Pages : 334
Book Description
This volume of Current Topics in Membranes focuses on Membrane Protein Crystallization, beginning with a review of past successes and general trends, then further discussing challenges of mebranes protein crystallization, cell free production of membrane proteins and novel lipids for membrane protein crystallization. This publication also includes tools to enchance membrane protein crystallization, technique advancements, and crystallization strategies used for photosystem I and its complexes, establishing Membrane Protein Crystallization as a needed, practical reference for researchers.
Author: Christopher B. Roth
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Author: Guillaume Lebon
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Author: Adriano D. Andricopulo
Author: Christian Holm
Author: Jean-Paul Renaud
Author: Sun Hongmao
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