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The book focuses on protein allostery in drug discovery. Allosteric regulation, ʹthe second secret of lifeʹ, fine-tunes virtually most biological processes and controls physiological activities. Allostery can both cause human diseases and contribute to development of new therapeutics. Allosteric drugs exhibit unparalleled advantages compared to conventional orthosteric drugs, rendering the development of allosteric modulators as an appealing strategy to improve selectivity and pharmacodynamic properties in drug leads. The Series delineates the immense significance of protein allostery—as demonstrated by recent advances in the repertoires of the concept, its mechanistic mechanisms, and networks, characteristics of allosteric proteins, modulators, and sites, development of computational and experimental methods to predict allosteric sites, small-molecule allosteric modulators of protein kinases and G-protein coupled receptors, engineering allostery, and the underlying role of allostery in precise medicine. Comprehensive understanding of protein allostery is expected to guide the rational design of allosteric drugs for the treatment of human diseases. The book would be useful for scientists and students in the field of protein science and Pharmacology etc.

Authored by the world's leading kinase experts, this is a comprehensive introduction to current knowledge and practice within this emerging field. Following an overview of the major players and pathways that define the kinome, the major part of this work is devoted to current strategies of kinome investigation and manipulation. As such, kinase engineering, peptide substrate engineering, co-substrate design and kinase inhibitor design are discussed in detail, and their potential applications in kinome analysis and kinome-based pharmacotherapy are shown. The result is a toolbox for every kinase researcher: By addressing and comparing current approaches to the study of kinase action, both novice and established researchers will benefit from the practical knowledge contained in this invaluable reference.

This book covers structure, function, and important roles of the SH domains, structure-function relationships, the versatile nature of their action, mechanisms of aggregation, specificity of interactions, impact of mutations on protein functional dysregulation, and cell signaling. Their involvement in various cellular processes such as migration, invasiveness, actin reorganization, shaping spines, determination of the morphology assembly of fibrils, and mechanotransduction makes these molecules attractive drug targets. Substrates, inhibitors and activators of PTKs present a wide variety of therapeutic agents in the context of delivering treatments for numerous pathologies. The new emerging field of stem cell therapies and design of biomaterials for treatments relies on the directed regulation of stem cell growth, differentiation and morphology, as well as the production of biomimetic scaffolds that respond to programmed signals. Advances in deciphering the mechanisms of action of these important molecules will lead to the implementation and success of their vital applications.

The functional characterization of a key enzyme in the phosphatidylinositol (PI) signaling pathway in the model plant Arabidopsis thaliana is the focus of the research summarised in this thesis. Moreover, a particular focus is the exploration of the biological functions of Arabidopsis phophatidylinositol monophosphate 5-kinase 2 (PIP5K2) which catalyzes the synthesis of phophatidylinositol (4,5) bisphosphate, the precursor of two important second messengers (inositol 1,4,5-trisphosphate and diacylglycerol). Through molecular and genetic approaches, the author isolated and characterized the expression pattern, physiological functions and the underlying mechanism of Arabidopsis PIP5K2. It is found that PIP5K2 is involved in regulating lateral root formation and root gravity response through modulating auxin accumulation and polar auxin transport and also plays a critical role in salt tolerance. These findings shed new light on the crosstalk between PI signaling and auxin response, both of which have crucial regulatory roles in plant development.

This book covers a variety of cutting-edge basic and clinical PAK research ranging from laboratory benches to hospital beds. The goal of this book is to inspire not only biomedical research scientists and university students, but also a variety of patients who suffer from PAK-dependent diseases and clinical doctors who try to cure or delay these PAK-dependent diseases.This book consists of 9 chapters which deal with different aspects of this kinase. These chapters are written by more than two dozen world-leading PAK experts. Each of these will provide updated biomedical information as well as future insight to a wide range of readers who are interested in this unique kinase and both its pathological and physiological roles as well as its functional evolution from its ancestral origins. - This publication will be the very first book ever published solely focused on PAK family kinases - Each chapter deals with the latest progress in PAK research written by a leading PAK expert with his or her own ideas and insight - Each chapter of this book has been written in such a way that clinical doctors who seek the effective cure of these formidable diseases, in addition to research scientists and biomedical students will value this book - This book describes in detail a number of PAK blockers which would be potentially useful for the therapy of these PAK-dependent diseases, and some of them are indeed available on the market inexpensively, without any side effect

Multicellular organisms must be able to adapt to cellular events to accommodate prevailing conditions. Sensory-response circuits operate by making use of a phosphorylation control mechanism known as the'two-component system.'This volume, the third in a three-volume treatment edited by the same group of editors, includes a wide range of methods, including those dealing with the Sln-1 kinase pathway, triazole sensitivity in C. albicans, and histidine kinases in cyanobacteria circadian clock. - Includes time-tested core methods and new innovations applicable to any researcher studing two-component signaling systems or histidine kinases - Methods included are useful to both established researchers and newcomers to the field - Relevant background and reference information given for procedures can be used as a guide to developing protocols in a number of disciplines

In this second of two new volumes covering mitochondria, methods developed to assess the number and function of nuclear-encoded proteins in the mitochondrion are presented. Chapters focus on the regulation of mitochondrial function and mitochondrial diseases, with a section emphasizing the mitochondrial defects associated with type 2 diabetes. The critically acclaimed laboratory standard for 40 years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. With more than 450 volumes published, each volume presents material that is relevant in today's labs, truly an essential publication for researchers in all fields of life sciences. - New methods focusing on the examination of normal and abnormal mitochondrial function are presented in an easy-to-follow format by the researchers who developed them - Along with a companion volume covering topics including mitochondrial electron transport chain complexes and reactive oxygen species, provides a comprehensive overview of modern techniques in the study of mitochondrial malfunction - Provides a'one-stop shop'for tried and tested essential techniques, eliminating the need to wade through untested or unreliable methods

Living cells are constantly sensing environmental changes, and their abilities to sense these changes and adapt to them are essential for their survival. In bacteria, histidine kinases are the major sensors for these environmental stresses, enabling cells to adapt to new growth conditions. Written by leading experts in the field, this book provides an up-to-date and comprehensive review on the structure and function of histidine kinases. It also provides extensive information on the physiological roles of histidine kinases in bacteria and eukaryotes. An an essential reference for cell biologists, microbiologists, molecular biologists, and biochemists interested in signal transduction. Experimental biologists and pharmacologists studying signal transduction systems in living organisms will also find it a valuable research tool. - The first comprehensive book on the roles of histidine kinases in cells - 23 in-depth chapters written by leading experts in the field - Describes the most recent advances in the field of signal transduction

As key components of many cell signaling pathways, protein kinases are implicated in a broad variety of diseases, including cancers and neurodegenerative conditions, and offer considerable potential as tractable targets for therapeutic intervention. In Protein Kinase Protocols, a panel of highly skilled laboratory investigators describe both basic and more sophisticated methods for the analysis of kinase-mediated signaling cascades, with emphasis on the identification of proteins according to their interactive relationships and the analysis of their functional properties. Described in step-by-step detail, these readily reproducible techniques offer novices quick access to a complicated field, and provide more experienced investigators many novel time-saving ploys. Emphasis is given to the critical technical steps that are often omitted from methods published in the primary literature. There are also tips on potential pitfalls and copious notes on how to adjust the protocols to work in related systems. Broad in its range of techniques and thoroughly detailed to help ensure experimental success, Protein Kinase Protocols offers both novice and experienced investigators powerful tools for understanding the functional roles of specific protein kinases within signaling cascades and for identification and evaluation of novel therapeutic targets.

Reversible phosphorylation is one of the major mechanisms of controlling protein activity in all eukaryotic cells. This new edition of Protein Phosphorylation: A Practical Approach provides a comprehensive description of current methods used to study protein phosphorylation and the kinases and phosphatases which catalyse it. It includes protocols for studying phosphorylation in intact cells; analysis of signal transduction pathways, kinase specificity, and kinase interactions; assay and purification of kinases and phosphatases; and identification of substrates. Also covered are cloning and expression protocols and advice on the crystallization of kinases and phosphatases. Protein Phosphorylation: A Practical Approach 2e will therefore be of great value to any researcher investigating aspects of reversible protein phosphrylation.

Protein phosphorylation is a key mechanism in cellular signaling. This volume presents a state-of-the-art survey of one of the most rapidly developing fields of biochemical research. Written by leading experts, it presents the latest results for some of the most important cellular pathways. Color plates illustrate structural or functional relationships, numerous references provide links to the original literature.

The Enzymes