Sirtuin Biology in Medicine: Targeting New Avenues of Care in Development, Aging, and Disease provides a fascinating and in-depth analysis of sirtuins in the body during normal physiology as well during disease highlighting the targeting of sirtuin-controlled pathways for the development of innovative, efficacious, and safe therapeutic strategies for multiple disorders in the body that ultimately can affect lifespan extension. Sirtuins are expressed throughout the body, have broad biological effects, and can significantly impact both cellular survival and longevity during acute and long-term illnesses. These histone deacetylases play an intricate role in the pathology, progression, and treatment of several disease entities ranging from neurodegenerative disorders, cardiovascular disease, immune system dysfunction, reproductive dysfunction, endocrine disorders, gastrointestinal disease, drug dependency, and aging-related disorders. Implementing a translational medicine format, this unique reference highlights novel signaling pathways for sirtuins that promote stem cell proliferation, enhance cellular protection, modulate pathways of apoptosis and autophagy, and extend life span. Each chapter is presented with insightful detail that will be of interest and a comprehensive resource to audiences that include scientists, physicians, pharmaceutical industry experts, nutritionists, and students.

New insights into modern medicine and systems biology are enabled by innovative protocols and advanced technologies in mass spectrometry-based proteomics. This volume details new pipelines, workflows, and ways to process data that allow for new frontiers in proteomics to be pushed forward. With applications to biomarker discovery, interactions between proteins, between biological systems, dynamics of post-translational modifications among others, new protocols have been developed and iteratively refined to probe the endless complexity of the proteome in ever greater details. This volume deals with methods for data dependent and data independent mass spectrometry analyses. Valuable, first-hand information is provided from designing experiments, sample preparation and analysis, exploitation of public datasets and carrying out reproducible data pipelines, using modern computational tools such as Galaxy or Jupyter. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Mass Spectrometry of Proteins: Methods and Protocols aims to ensure successful results in the further study of this vital field.

Daniel C. Liebler masterfully introduces the science of proteomics by spelling out the basics of how one analyzes proteins and proteomes, and just how these approaches are then employed to investigate their roles in living systems. He explains the key concepts of proteomics, how the analytical instrumentation works, what data mining and other software tools do, and how these tools can be integrated to study proteomes. Also discussed are how protein and peptide separation techniques are applied in proteomics, how mass spectrometry is used to identify proteins, and how data analysis software enables protein identification and the mapping of modifications. In addition, there are proteomic approaches for analyzing differential protein expression, characterizing proteomic diversity, and dissecting protein-protein interactions and networks.

New insights into the evolution and nature of proteins

Exploring several distinct approaches, this book describes the methods for comparing protein sequences and protein structures in order to identify homologous relationships and classify proteins and protein domains into evolutionary families. Readers will discover the common features as well as the key philosophical differences underlying the major protein classification systems, including Pfam, Panther, SCOP, and CATH. Moreover, they'll discover how these systems can be used to understand the evolution of protein families as well as understand and predict the degree to which structural and functional information are shared between relatives in a protein family.

Edited and authored by leading international experts, "Protein Families "offers new insights into protein families that are important to medical research as well as protein families that help us understand biological systems and key biological processes such as cell signaling and the immune response. The book is divided into three sections: Section I: Concepts Underlying Protein Family Classification reviews the major strategies for identifying homologous proteins and classifying them into families.Section II: In-Depth Reviews of Protein Families focuses on some fascinating super protein families for which we have substantial amounts of sequence, structural and functional data, making it possible to trace the emergence of functionally diverse relatives.Section III: Review of Protein Families in Important Biological Systems examines protein families associated with a particular biological theme, such as the cytoskeleton.

All chapters are extensively illustrated, including depictions of evolutionary relationships. References at the end of each chapter guide readers to original research papers and reviews in the field.

Covering protein family classification systems alongside detailed descriptions of select protein families, this book offers biochemists, molecular biologists, protein scientists, structural biologists, and bioinformaticians new insight into the evolution and nature of proteins.

This new edited volume in the Springer Subcellular Biochemistry Series presents a comprehensive, state-of-the-art overview of the proteomics of peroxisomes derived from mammalian, Drosophila, fungal, and plant origin, and contains contributions from leading experts in the field. The development of sensitive proteomics and mass spectrometry technologies, combined with bioinformatics approaches now allow the identification of low-abundance and transient peroxisomal proteins and permits to identify the complete proteome of peroxisomes, with the consequent increase of our knowledge of the metabolic and regulatory networks of these important cellular organelles. The book lines-up with these developments and is organized in four sections including: (i) mass spectrometry-based organelle proteomics; (ii) prediction of peroxisomal proteomes; (iii) analysis of peroxisome proteome interaction networks; and (iv) peroxisomes in relation to other subcellular compartments. The editor Luis A. del Rio is Professor ad honorem of the Spanish National Research Council (CSIC) in the Group of Antioxidants, Free Radicals and Nitric Oxide in Biotechnology, Food and Agriculture, Department of Biochemistry and Cell & Molecular Biology of Plants, at the Estacion Experimental del Zaidin, Granada, Spain. Del Rio's research group focuses on the metabolism of reactive oxygen species (ROS), reactive nitrogen species (RNS) and antioxidants in plant peroxisomes, and the ROS- and RNS-dependent role of peroxisomes in plant cell signalling. The editor Michael Schrader is Professor of Cell Biology & Cytopathology in the Department of Biosciences at the University of Exeter, UK. Using mammalian peroxisomes as model organelles, Prof. Schrader and his team aim to unravel the molecular machinery and signalling pathways that mediate and regulate the formation, dynamics and abundance of these medically relevant cellular compartments.

Lectins have in the past been regarded by many scientists as curious proteins of uncertain structure and specificity that bind to carbohydrates of dubious significance themselves. All this is rapidly changing. The functional importance of glycosylation in cell-cell and cell-pathogen interactions, as well as intracellular events, has been recognized by the explosion of the science of glycobiology. This has been paralleled by the realization that lectins, once they have been well characterized, can be extremely useful tools for exam- ing structural changes in glycosylation and their functional consequences for human pathophysiology. Different lectins vary considerably in their degree of specificity. Some, such as wheatgerm agglutinin, have fairly broad specificity (for glucosamine or sialic acid), whereas others, such as Maackia amurensis, are specific not only for a single carbohydrate, but also for its linkage (2-3 linked sialic acid). Lectins with relatively broad specificity may be very useful as an adjunct to isolation or quantification of soluble glycoproteins, whereas lectins of known, and precise, specificity will be more useful for characterization of carbo- drate structure. We have included an appendix in Lectin Methods and Pro- cols that provides the known specificities of all lectins cited in the text.

A Unified Microscopic Approach to Analyzing Complex Processes in Molecular Motors Motor Proteins and Molecular Motors explores the mechanisms of cellular functioning associated with several specific enzymatic molecules called motor proteins. Motor proteins, also known as molecular motors, play important roles in living systems by supporting cellular transport and force generation via the transformation of chemical energy into mechanical work. The book presents established results, theoretical methods, and experimental observations related to biological molecular motors. It uses fundamental physical-chemical concepts and methods to develop a systematic theoretical framework for understanding motor protein dynamics. The author introduces the main ideas using simple arguments that avoid heavy mathematical derivations in favor of more intuitive physical understanding. Although the book assumes some rudimentary knowledge of cell biology, calculus, and basic ideas from chemistry and physics, it gives explanations and derivations for most results. Accessible to students and researchers in a wide range of scientific fields, this book provides a unified molecular picture for analyzing motor proteins. It connects major experimental facts on molecular motors to principal theoretical concepts consistent with the fundamental laws of chemistry and physics.

The edition details methods to study intrinsically disordered proteins (IDPs) including recent topics such as extremely high-affinity disordered complexes, kinetics that evade established concepts, liquid-liquid phase separation, and novel disorder-driven allosteric mechanisms. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Intrinsically Disordered Proteins: Methods and Protocols aims to help scientists with different backgrounds to further their investigations into these fascinating and dynamic molecules. Chapter 24 is available open access under a CC BY 4.0 license via link.springer.com. Chapters "40 and 42 " are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

With the invitation to edit this volume, I wanted to take the opportunity to assemble reviews on different aspects of circadian clocks and rhythms. Although most c- tributions in this volume focus on mammalian circadian clocks, the historical int- duction and comparative clocks section illustrate the importance of various other organisms in deciphering the mechanisms and principles of circadian biology. Circadian rhythms have been studied for centuries, but only recently, a mole- lar understanding of this process has emerged. This has taken research on circadian clocks from mystic phenomenology to a mechanistic level; chains of molecular events can describe phenomena with remarkable accuracy. Nevertheless, current models of the functioning of circadian clocks are still rudimentary. This is not due to the faultiness of discovered mechanisms, but due to the lack of undiscovered processes involved in contributing to circadian rhythmicity. We know for example, that the general circadian mechanism is not regulated equally in all tissues of m- mals. Hence, a lot still needs to be discovered to get a full understanding of cir- dian rhythms at the systems level. In this respect, technology has advanced at high speed in the last years and provided us with data illustrating the sheer complexity of regulation of physiological processes in organisms. To handle this information, computer aided integration of the results is of utmost importance in order to d- cover novel concepts that ultimately need to be tested experimentally.

This book describes hydration structures of proteins by combining experimental results with theoretical considerations. It is designed to introduce graduate students and researchers to microscopic views of the interactions between water and biological macromolecules and to provide them with an overview of the field. Topics on protein hydration from the past 25 years are examined, most of which involve crystallography, fluorescence measurements, and molecular dynamics simulations. In X-ray crystallography and molecular dynamics simulations, recent advances have accelerated the study of hydration structures over the entire surface of proteins. Experimentally, crystal structure analysis at cryogenic temperatures is advantageous in terms of visualizing the positions of hydration water molecules on the surfaces of proteins in their frozen-hydrated crystals. A set of massive data regarding hydration sites on protein surfaces provides an appropriate basis, enabling us to identify statistically significant trends in geometrical characteristics. Trajectories obtained from molecular dynamics simulations illustrate the motion of water molecules in the vicinity of protein surfaces at sufficiently high spatial and temporal resolution to study the influences of hydration on protein motion. Together with the results and implications of these studies, the physical principles of the measurement and simulation of protein hydration are briefly summarized at an undergraduate level. Further, the author presents recent results from statistical approaches to characterizing hydrogen-bond geometry in local hydration structures of proteins. The book equips readers to better understand the structures and modes of interaction at the interface between water and proteins. Referred to as "hydration structures", they are the subject of much discussion, as they may help to answer the question of why water is indispensable for life at the molecular and atomic level.

Starting from a comprehensive quantum mechanical description, this book introduces the optical (IR, Raman, UV/Vis, CD, fluorescence and laser spectroscopy) and magnetic resonance (1D and 2D-NMR, ESR) techniques. The book offers a timely review of the increasing interest in using spin-label ESR as an alternative structural technique for NMR or X-ray diffraction. Future aspects are treated as well, but only as an illustration of the progress of ESR in this field.

This book summarizes all the important aspects of CRLs (Cullin-RING E3 Ubiquitin Ligases), while providing details of mechanistic specifics that go beyond protein ubiquitination and neddylation. Ubiquitin ligases, including the CRLs, which are activated by neddylation, play an important role in diverse biological processes and are involved in various human diseases, particularly cancer. The book covers various topics, such as CRL structure, biology, genetics, its regulation by neddylation, its pivotal role in human disease, and its potential in drug discovery and targeted therapies. The book appeals to biochemists and biologists working in other fields, and, given the importance of CRLs in all aspects of cell biology and the great promise of targeting these complexes for therapy, is a valuable resource anyone interested in modern biology or medicine.

Prognostic and Therapeutic Applications of RKIP in Cancer provides updated reviews on the chemistry, signaling, pre-clinical and clinical activities, and role of RKIP expression levels for diagnostics, prognosis and potential interventions. The development of novel compounds and conjugates that selectively induce RKIP expression in cancer open a novel era of new therapeutics and their potential in the treatment of highly resistant cancers and metastases. Edited and written by internationally renowned experts in the field of novel therapeutics for cancer, this book is a valuable source for cancer researchers, medical scientists, clinicians, clinical pharmacologists, and graduate students.

Understanding Biology Using Peptides: Proceedings of the 19th American Peptide Symposium highlights many of the recent developments in peptide science, with a particular emphasis on how these advances are being applied to basic problems in biology and medicine. Specific topics covered include novel synthetic strategies, peptides in biological signaling, post-translational modifications of peptides and proteins, peptide quaternary structure in material science and disease, and peptides as tools in drug discovery.

About the Editor:

Dr. Sylvie Blondelle is an Associate Member in Microbiology/Biochemistry at Mixture Science, Inc., San Diego, CA and Head of the Biosafety Department at the Burnham Institute for Medical Research. Her research focuses on strategies toward the development an HIV vaccine through optimization of peptide immunogens. Dr. Blondelle received her Ph.D. in organic chemistry from the University of Montpellier, France, in 1988.

There are 28 different collagens, with 46 unique chains, which allows for a collagen for each time and place. Some collagens are specialized for basement membrane, whereas others are the central structural component of the interstitial matrix. There are eight collagens among the 20 most abundant proteins in the body, which makes these molecules essential building blocks of tissues. In addition, lessons learned from monogenomic mutations in these proteins result in grave pathologies, exemplifying their importance in development. These molecules, and their post-translationally modified products serve as biomarkers of diseases in a range of pathologies associated with the extracellular matrix. Biochemistry of Collagens, Laminins, and Elastin: Structure, Function, and Biomarkers, Second Edition provides researchers and students current data on key structural proteins (collagens, laminins, and elastin), reviews on how these molecules affect pathologies, and information on how selected modifications of proteins can result in altered signaling properties of the original extracellular matrix component. Further, it discusses the novel concept that an increasing number of components of the extracellular matrix harbor cryptic signaling functions that may be viewed as endocrine function, and it highlights how this knowledge can be exploited to modulate fibrotic disease.

Protein Modificomics: From Modifications to Clinical Perspectives comprehensively deals with all of the most recent aspects of post-translational modification (PTM) of proteins, including discussions on diseases involving PTMs, such as Alzheimer's, Huntington's, X-linked spinal muscular atrophy-2, aneurysmal bone cyst, angelman syndrome and OFC10. The book also discusses the role PTMs play in plant physiology and the production of medicinally important primary and secondary metabolites. The understanding of PTMs in plants helps us enhance the production of these metabolites without greatly altering the genome, providing robust eukaryotic systems for the production and isolation of desired products without considerable downstream and isolation processes.

Driven by the widespread growth of proteomic practices, protein separation techniques have been refined to minimize variability, optimize particular applications, and adapt to user preferences in the analysis of proteins. Separation Methods in Proteomics provides a comprehensive examination of all major separation techniques for proteomics research. Written as a compilation of hands-on methods exemplified by the work of several recognized leaders in the field, this book may serve as a guide for selection of the optimal separation strategies to solve particular biological problems. Recent progress in the development of robust analytical techniques and instrumentation has created the need for good quality biological samples that are subject to analysis. Emphasizing the importance of sample preparation, the book explains how proteomes can be divided into smaller, less complicated "subproteomes" for individual analysis. It also highlights several hybrid approaches that take into account protein interactions. Including applications of the separation methods currently employed in proteomic analyses for both clinical and basic research, Separation Methods in Proteomics contains practical information that can enhance the current and future endeavors of scientists in proteomics, genomics, transcriptomics, biomarker discovery, and drug discovery.

Using a geometric perspective, Protein Geometry, Classification, Topology, and Symmetry reviews and analyzes the structural principals of proteins with the goal of revealing the underlying regularities in their construction. It also reviews computer methods for structure analysis and the automatic comparison and classification of these structures with an analysis of the statistical significance of comparing different shapes. Following an analysis of the current state of protein classification, the authors explore more abstract geometric and topological representations, including the occurrence of knotted topologies. The book concludes with a consideration of the origin of higher-level symmetries in protein structure. The authors focus on simple geometric methods that are deterministic rather than probabilistic and on the more abstract simplifications of protein structure that allow a better understanding of the overall fold of the structure. Most of the methods described in this book have corresponding computer programs. These can be found (as C source code) at the ftp site of the Division of Mathematical Biology at the National Institute for Medical Research. This collection of ideas contains pedagogical material that make it ideal for post-graduate courses as well as new ideas and results essential for researchers investigating protein structures.

Although less common than -amino acids, non- -amino acids-where the amino group is not on the carbon immediately adjacent to the carboxyl group but is attached to another carbon in the chain (for example, the , , carbon)-are components of biologically important molecules, are significant in the pharmaceutical industry, and are useful starting materials for many areas of organic chemistry. Since the publication of the first edition of this book nearly 20 years ago, synthetic work devoted to the preparation of non- -amino acids has expanded greatly. Methods of Non- -Amino Acid Synthesis, Second Edition has been extensively rewritten and reorganized, providing an up-to-date review of strategies and methods for non- -amino acid synthesis, particularly those amino acids that are key synthetic intermediates or important compounds in their own right. It focuses on acyclic amino acids of C3-C10, but also aminoalkanoic carboxylic acids, aminoalkenoic acids, and aminoalkynoic acids. The new edition contains many updated references and has a greater emphasis on the biological importance of non- -amino acids. In addition to an array of synthetic methods, the book offers discussions on why non- -amino acids are important. The book covers synthetic methods that rely on substituent refunctionalization, the conversion of cyclic precursors to acyclic amino acids, conjugate addition reactions, and enolate anion reactions and condensation reactions that lead to non- -amino acids. It also examines reactions and strategies that lead to good diastereoselectivity and enantioselectivity during synthesis. A chapter devoted to biologically important amino acids includes separate sections on GABA, GABOB, carnitine, DAVA, statine, and other significant amino acids as well as a new section on peptides and proteins that contain non- -amino acids. The final chapter addresses aminocyclic and heterocyclic amino acids.

Offers coverage of the development of protein purification processes for large-scale commercial operations, and addresses process development, scale-up, applications and mathematical descriptions. Technologies currently used at the commercial scale are covered in depth.

Introduction to Computational Proteomics introduces the field of computational biology through a focused approach that tackles the different steps and problems involved with protein analysis, classification, and meta-organization. The book starts with the analysis of individual entities and works its way through the analysis of more complex entities, from protein families to interactions, cellular pathways, and gene networks. The first part of the book presents methods for identifying the building blocks of the protein space, such as motifs and domains. It also describes algorithms for assessing similarity between proteins based on sequence and structure analysis as well as mathematical models, such as hidden Markov models and support vector machines, that are used to represent protein families and classify new instances. The second part covers methods that investigate higher order structure in the protein space through the application of unsupervised learning algorithms, such as clustering and embedding. The book also explores the broader context of proteins. It discusses methods for analyzing gene expression data, predicting protein-protein interactions, elucidating cellular pathways, and reconstructing gene networks. This book provides a coherent and thorough introduction to proteome analysis. It offers rigorous, formal descriptions, along with detailed algorithmic solutions and models. Each chapter includes problem sets from courses taught by the author at Cornell University and the Technion. Software downloads, data sets, and other material are available at biozon.org

This book, a consecutive contribution to the series Challenges and Advances in Computational Chemistry and Physics, focuses on understanding the photoinduced processes in biological systems. Understanding and fine control of light fate in molecules is vital for the progress of society and environmental safety. Light induced changes of various physico-chemical and spectroscopic properties in nucleic acids and proteins is the basis of fundamental biological events such as vision, DNA photodamage or photosensing. The investigation of these processes is challenging to both theoretical and experimental studies. This volume encompasses the quantum mechanics/molecular mechanics theory in several subfields, including: advanced computational methods for nucleic acids and proteins systems; dynamics, spectroscopic and physico-chemical properties of biological photoreceptors; DNA photodamage. This book is of interest to readers in both fundamental and application-oriented research by overviewing recent achievements in computational modeling of excited states in nucleic acids and proteins.

"Amino Acid Metabolism, 3rd Edition" covers all aspects of the biochemistry and nutritional biochemistry of the amino acids. Starting with an overview of nitrogen fixation and the incorporation of inorganic nitrogen into amino acids, the book then details other major nitrogenous compounds in micro-organisms, plants and animals. Contents include a discussion of the catabolism of amino acids and other nitrogenous compounds in animals, and the microbiological reactions involved in release of nitrogen gas back into the atmosphere. Mammalian (mainly human) protein and amino acid requirements are considered in detail, and the methods that are used to determine them.

Chapters consider individual amino acids, grouped according to their metabolic origin, and discussing their biosynthesis (in plants and micro-organisms for those that are dietary essentials for human beings), major metabolic roles (mainly in human metabolism) and catabolism (again mainly in human metabolism). There is also discussion of regulatory mechanisms for all these metabolic pathways, and of metabolic and genetic diseases affecting the (human) metabolism of amino acids.

Throughout the book the emphasis is on the nutritional importance of amino acids, integration and control of metabolism and metabolic and other disturbances of relevance to human biochemistry and health. Completely revised edition of this comprehensive text covering all the latest findings in amino acid metabolism researchWritten by an authority in the field Covers new advances in structural biologyClear illustrations of all structures and metabolic pathwaysFull list of recommended further reading for each chapter and bibliography of papers cited in the text

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 and their involvement in various human diseases. The book presents current approaches in drug discovery that include target selection, establishment of screening and functional assays. It also covers recombinant GPCR expression for drug screening and structural biology, different methods for structural characterization of GPCRs, and the importance of bioinformatics. The book has been carefully edited to avoid overlapping information, some duplication has been intentionally permitted so that each chapter can function as an independent unit. Providing in-depth discussions on structure and dynamics of GPCRs, this book outlines the importance of the GPCRs to drug discovery in general and drug targets specifically. Daniel E. Levy, editor of the Drug Discovery Series, is the founder of DEL BioPharma, a consulting service for drug discovery programs. He also maintains a blog that explores organic chemistry.

The rapid advances in recombinant DNA technology and the increasing availability of peptides and proteins with therapeutic potential are a challenge for pharmaceutical scientists who have to formulate these compounds as drug products.

Pharmaceutical Formulation Development of Peptides and Proteins, Second Edition discusses the development of therapeutic peptides and proteins, from the production of active compounds via basic pre-formulation and formulation to the registration of the final product.

Providing integrated solutions, this book discusses:

• The synthesis of peptides and the biotechnological production of proteins through recombinant DNA technology
• The physicochemical characteristics and stability of peptides and proteins
• The formulation of proteins as suspensions, solutions, and (mostly freeze-dried) solids
• The opportunities and challenges of non-parenteral delivery of peptides and proteins
• Risk factors, specifically the development of an unwanted immune response
• A simulation approach to describe the fate of peptides and proteins upon administration to a biological system
• The documentation required to register a protein-based drug

Scientists in the pharmaceutical industry and academia as well as postgraduate students in pharmaceutical science will find this a valuable resource.