Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

This brief introduces the structural and functional characterization of this important group of proteins. The content of each chapter is aimed at the non-specialist so that key concepts, methodologies and applications can be presented in a "snapshot" style volume. Multiheme cytochromes are ever more important now that it is possible to obtain genome sequences of microorganisms which have major biotechnological and environmental implications. There is a tremendous profusion of multiheme cytochromes which have great potential as targets for bioremediation and bioenergy applications. This brief gives a glimpse of an intriguing and fast-moving field.

This book provides a detailed description and analysis of the reduction and metabolism of metals and metalloids by sulfate reducing bacteria. The molecular mechanisms of bacterial resistance to copper are examined as well as extracellular electron transfer and bacterial metal oxide respiration. Furthermore, in this book enrichment, isolation, and physiology of magnetotactic bacteria are discussed.  The interactions of bacteria with metals in natural environments and their role in metal cycling have been studied for decades. Advances in studies of bacteria-metal interactions identified numerous important aspects of these interactions, such as bioremediation of metal-contaminated environments, the role of metals in redox reactions and other cellular functions, as well as the role of metals in toxicity and infection. Microbiologists, environmental scientists, and students interested in microbe interactions with metals and their effect on the environment and their application in biotechnology will be interested in the topics discussed in the book.

Based upon a workshop entitled “The Small HSP World� held in Québec 2-5 October 2014. Twenty-five scientists provided chapters for the book. The chapters are from the best scientists currently working in this field.  These colleagues include Arrigo, Benesch, Benjamin, Buchner-Haslbeck-Weinkauf, Benndorf, Boelens, Carra, Chang, Currie, Ecroyd, Emanuelsson, Fu, Garrido, Golenhofen, Gusev, Hightower, Kampinga, Lavoie, MacRae, Quinlan, Tanguay, Vierling, Vigh, Weeks and Wu. Briefly, the book starts with the structure of small heat shock proteins, moving to their functions and finishing with their involvement in diseases. Although this is quite broad, the structural aspect will be the unifying theme of the book.

Proteins are the cell's workers, their messengers and overseers. In these roles, proteins specifically bind small molecules, nucleic acid and other protein partners. Cellular systems are closely regulated and biologically significant changes in populations of particular protein complexes correspond to very small variations of their thermodynamics or kinetics of reaction. Interfering with the interactions of proteins is the dominant strategy in the development of new pharmaceuticals. Protein Ligand Interactions: Methods and Applications, Second Edition provides a complete introduction to common and emerging procedures for characterizing the interactions of individual proteins. From the initial discovery of natural substrates or potential drug leads, to the detailed quantitative understanding of the mechanism of interaction, all stages of the research process are covered with a focus on those techniques that are, or are anticipated to become, widely accessible and performable with mainstream commercial instrumentation. Written in the highly successful Methods in Molecular Biology series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Protein Ligand Interactions: Methods and Applications, Second Edition serves as an ideal guide for researchers new to the field of biophysical characterization of protein interactions - whether they are beginning graduate students or experts in allied areas of molecular cell biology, microbiology, pharmacology, medicinal chemistry or structural biology.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

A common approach to understanding the functional repertoire of a genome is through functional genomics. With systems biology burgeoning, bioinformatics has grown to a larger extent for plant genomes where several applications in the form of protein-protein interactions (PPI) are used to predict the function of proteins. With plant genes evolutionarily conserved, the science of bioinformatics in agriculture has caught interest with myriad of applications taken from bench side to in silico studies. A multitude of technologies in the form of gene analysis, biochemical pathways and molecular techniques have been exploited to an extent that they consume less time and have been cost-effective to use. As genomes are being sequenced, there is an increased amount of expression data being generated from time to time matching the need to link the expression profiles and phenotypic variation to the underlying genomic variation. This would allow us to identify candidate genes and understand the molecular basis/phenotypic variation of traits. While many bioinformatics methods like expression and whole genome sequence data of organisms in biological databases have been used in plants, we felt a common reference showcasing the reviews for such analysis is wanting. We envisage that this dearth would be facilitated in the form of this Springer book on Agricultural Bioinformatics. We thank all the authors and the publishers Springer, Germany for providing us an opportunity to review the bioinformatics works that the authors have carried in the recent past and hope the readers would find this book attention grabbing.  

Lipid peroxidation is an important cellular process which can lead to detrimental effects if it is not regulated efficiently. Lipid hydroperoxide is formed in an initial step of lipid peroxidation. Lipid hydroperoxide is also known as a potential source of singlet oxygen. Harmful aldehydes are formed when the lipid hydroperoxide is degraded. The formed aldehyde has high reactivity against thiol or amine moieties. Therefore, it could act as a signaling molecule, which might induce the changing of gears inside a cell. Recent studies have shown that lipid hydroperoxide or a slightly modified product of the lipid hydroperoxide reacts with biomolecules such as proteins and aminophospholipids, which leads to formation of amide-type adducts. Amide-type adducts could be one of markers for oxidative stress and could also be an important player in some diseases. In this book, the chemistry and biochemistry of lipid hydroperoxide along with their conjugates with biomolecules are described.

Photoswitching Proteins: Methods and Protocols, focuses on proven applications of photoswitching proteins in cell and neurobiology. Optical approaches have been mostly embraced by the neurosciences to allow fast, high-resolution characterization and manipulation of single cells in complex neuronal tissue. These tools, including photoswitching of proteins, are now successfully used in almost all fields of biological research. 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 key tips on troubleshooting and avoiding known pitfalls.Comprehensive and practical, Photoswitching Proteins: Methods and Protocols highlights many of the possibilities for research based on light-inducible, high-resolution manipulation of biological systems.

Cancer Genomics and Proteomics: Methods and Protocols, Second Edition includes methods for the analyses of cancer genome and proteome that have illuminated us about the changes in cancer cells. 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 key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Cancer Genomics and Proteomics: Methods and Protocols, Second Edition seeks to aid scientists in the further study into various aspects of tumor initiation and progression.

Plant Proteomics: Methods and Protocols, Second Edition presents recent advances made in the field of proteomics and their application to plant biology and translational research. In recent years, improvements in techniques and protocols for high-throughput proteomics have been made at all workflow stages, from wet (sampling, tissue and cell fractionation, protein extraction, depletion, purification, separation, MS analysis, quantification) to dry lab (experimental design, algorithms for protein identification, bioinformatics tools for data analysis, databases, and repositories). Divided into nine convenient sections, chapters cover topics such as applications of gel-free, label- or label-free, imaging and targeted approaches to experimental model systems, crops and orphan species, as well as the study and analysis of PTMs, protein interactions, and specific families of proteins, and finally proteomics in translational research. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Plant Proteomics: Methods and Protocols, Second Edition seeks to serve both professionals and novices looking to exploit the full potential of proteomics in plant biology research.

For many years, the authors have investigated the adaptive role of heat shock proteins (HSPs) in different animals, including the representatives of homothermic and poikilothermic organisms that inhabit regions with contrasting thermal conditions. This book will summarize the data accumulated in the course of these studies and describe the general molecular mechanisms underlying the adaptation of various organisms to aggressive environments. We also concentrate on different evolutionary trends characteristic for HSP systems in the course of adaptation to fluctuating environmental conditions. In addition, we describe the peculiarities in the regulatory regions of heat shock genes necessary for fine tuning of these systems providing the adaptation to adverse conditions. Special emphasis is given to the role of mobile elements in the evolution and functioning of various groups of HSP genes. The book combines the results of field studies and laboratory analysis of stress genes systems.

Maize is a globally important crop mainly utilized as feed, food and raw material for diverse industrial applications. Among cereals, it occupies third place after rice and wheat and is a staple food for a large segment of population worldwide particularly in the Asian as well as African countries. This monogram discusses various aspects of nutritional quality of maize such as quality protein maize which has been considered as most significant discovery in enhancing nutritional quality of cereals in terms of increasing the concentration of essential amino acids. The biochemistry of starch which is an important industrial product of maize has been discussed in detail. Further, the role of maize oil which is highly regarded for human consumption as it reduces the blood cholesterol concentration has also been elaborated. Naturally, maize is a rich source of carotenoids such as beta-carotene, zeaxanthin, lutein, cryptoxanthin which have highly diverse health benefits ranging from maintaining normal vision to lowering of oxidative stress. The need for biofortification of maize for provitamin A carotenoids and their role in alleviating vision impairments have also been discussed. The effect of various biotic and abiotic stresses particularly carbon dioxide and temperature on quality has been discussed thoroughly. Many value-added products as well as fermented foods that have been produced from maize which is consumed in different forms worldwide are also discussed. The aspects related to the maize application as fodder and as a source of malting have also been covered concisely. Overall, the book provides complete information about various quality aspects of maize. The various stakeholders such as maize researchers, extension specialists, students, teachers as well as farmers will be immensely benefitted from this monogram.

In a simplified form, epigenetics refers to heritable changes in phenotype that are not due to changes in the underlying DNA sequence. In this book, epigenetic mechanisms of regulation and dysregulation in health and disease are explored in great depth. Detailed chapters on epigenetic processes including DNA methylation and chromatin post-translational modifications including potential interventions with DNA methyltransferase inhibitors and histone deacetylase inhibitors are explored in initial chapters. These provide a detailed overview and important background to the entire field. The book is then focussed on epigenetic mechanisms involved in various diseases including anti-inflammatory and autoimmune conditions. Important accounts relating to the effects of epigenetics in metabolic syndrome, cardiovascular disease and asthma are the focus of subsequent chapters. The role of epigenetic dysregulation in malignancy is a current topic of interest and represents an intense field of research. A large component of this book is dedicated to the analysis of aberrant epigenetic processes in carcinogenesis and cancer progression. Further, chapters are focused on emerging cancer prevention using nutritional components and anti-cancer therapies particularly with histone deacetylase inhibitors, which have already been approved for the treatment of cutaneous T-cell lymphoma. The emerging role of nanoparticle preparations, especially in the context of delivering potential epigenetic therapies to target cells in various diseases, is also explored in this book. Overall, this book encompasses a wide range of topics related to epigenetic mechanisms in health and disease and would appeal to anyone with an interest in epigenetics, chromatin biology and emerging epigenetic interventions and therapies.

Receptor Tyrosine Kinases: Methods and Protocols explores on the most widely studied of the protein classes, known for their central role in several cellular functions and in a variety of human pathologies. Beginning with a section on activation and signaling of Receptor Tyrosine Kinases (RTKs), the book continues with chapters on aberrant expression of RTKs, trafficking and negative regulation, as well as RTKs as pharmacological targets. 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, laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Receptor Tyrosine Kinases: Methods and Protocols contains an up-to-date overview of the most relevant and widely used methods employed in this field, providing detailed protocols that molecular and cellular biologists could easily adopt in their research programs on RTKs.

Molecular chaperones are a fundamental group of proteins that have been identified only relatively recently. They are key components of a protein quality machinery in the cell which insures that the folding process of any newly-synthesized polypeptide chain results in the formation of a properly folded protein and that the folded protein is maintained in an active conformation throughout its functional lifetime. Molecular chaperones have been shown to play essential roles in cell viability under both normal and stress conditions. Chaperones can also assist in the unfolding and degradation of misfolded proteins and in disaggregating preformed protein aggregates. Chaperones are also involved in other cellular functions including protein translocation across membranes, vesicle fusion events, and protein secretion. In recent years, tremendous advances have been made in our understanding of the biology, biochemistry, and biophysics of function of molecular chaperones. In addition, recent technical developments in the fields of proteomics and genomics allowed us to obtain a global view of chaperone interaction networks. Finally, there is now a growing interest in the role of molecular chaperones in diseases. This book will provide a comprehensive analysis of the structure and function of the diverse systems of molecular chaperones and their role in cell stress responses and in diseases from a global network perspective.

This book provides a timely review of the role of histone modifications in epigenetic control of gene expression. Topics covered include: basic mechanisms of molecular recognition of histone post-translational modification (PTMs); combinatorial readout of histone PTMs by tandem epigenome reader domains; genome-wide profiling of histone PTM interactions; small molecule modulation of histone PTM interactions and their potential as a new approach to therapeutic intervention in human diseases. All chapters were written by leading scientists who made the original key discoveries of the structure and mechanism of evolutionarily conserved reader domains, which serve to direct gene transcription in chromatin through interactions with DNA-packing histones in a PTM-sensitive manner.

The main purpose of this volume is to provide a focused analysis of the function of the G protein-coupled signaling pathways that operate in the interconnected network of retinal neurons as they detect and encode the information carried by light. The organization of this volume will generally follow the path of signal flow in the retina. First we will describe recent advances in understanding the phototransduction cascade of rod and cone photoreceptors, which use signaling cascade based on the GPCR rhodopsin to transduce incident light into neural activity. Chapters will be devoted to unique specializations of the two major types of photosensitive cells that comprise the predominant input for our spatial and color vision. Subsequently, the mechanisms of synaptic information encoding by retinal ON bipolar cells will be described, where the GPCR mGluR6 plays a fundamental role. Chapters in this section will examine macromolecular organization of the mGluR6 signaling pathway as well as current understanding of its function. The functional characteristics of this signaling mechanism will be explored in detail. Additionally, this section will cover the role of dopamine receptors in modulating signal transmission between photoreceptors and ON-bipolar cells. Finally, chapters will be focused on the output neurons of the inner retina, ganglion cells, where the components of the emerging GPCR melanopsin cascade in intrinsically photosensitive ganglion cells will be detailed. Collectively these mechanisms allow the retina to represent visual space over a wide range of light intensities.

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.

Non-vesicular intracellular cholesterol transport is an important mechanism for maintaining membrane cholesterol homeostasis. Recent reports of studies directed at soluble cholesterol transport proteins indicate that aberrant expression of the START proteins may contribute to disease states associated with disorders in cholesterol homeostasis. This is an exciting new direction in the field and the purpose of this book will be to highlight the current research directed at potential roles for the START family in diabetes, cancer and atherogenesis. This book also provides a personal and historical perspective of the discovery-to-publication journey that the authors had for their particular START domain family member. The goal will be to provide perspectives to graduate students, post-doctoral fellows and endocrinology fellows on the research discovery process.

Squamous cell cancers of the head and neck (SCCHN), also known as head and neck cancers (HNC) encompass malignancies of the oral cavity, larynx, nasopharynx and pharynx, and are diagnosed in over 500,000 patients worldwide each year, accounting for 5% of all malignancies. In the past several years, there have been significant developments in understanding of HNC. It is now recognized that although alcohol and tobacco use has represented the likely predominant cause of SCCHN, the incidence of a second class of SCCHN related to oncogenic human papillomavirus (HPV) infection is increasing, with a four-fold increase in the past 2 decades, and now thought to represent up to 30% of cases. The first effective target for SCCHN, the EGFR-targeting antibody cetuximab, was approved as recently as in 2006; since then, a growing body of research has identified additional signaling pathways as important in disease pathogenesis, and in resistance to treatment. Proteins such as c-Met, Src, and HER2 are emerging as new therapeutic targets, with a considerable ferment in the clinical trial community. As a capstone of research progress, 2011 marked the first reports of high throughput sequencing of SCCHN tumors, with these efforts identifying unexpected players such as Notch as frequent subject of mutation, spawning new hypotheses for future research. This book will be of interest to researchers who are interested in better understanding the biology of head and neck cancers, with the goals of better designing therapies, identifying risk factors, or investigating the molecular basis of the disease.

This book will focus on new molecular interactions and novel activities and the associated diseases that have been recently discovered from the studies of eukaryotic and mammalian aminoacyl-tRNA synthetases. In addition, the potential applications of ARS researches in biotechnology and medicine will be addressed.

Metalloproteins are involved in many key biological processes such as gas transport and metabolism, photosynthesis, cell respiration, the Krebs cycle and many other vital redox reactions. Metalloproteins: Methods and Protocols addresses multiple aspects of metalloenzyme research from the production and purification of metalloproteins using both standard recombinant techniques and a cell-free system, to the electrochemical analysis of metalloproteins, as well as IR techniques, Moessbauer spectroscopy and the theoretical interpretation of metalloenzyme catalytic and redox processes, to name a few topics. Written in the 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 protocols and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Metalloproteins: Methods and Protocols seeks to serve both professionals and novices interested in the metalloprotein field.

This book updates the latest development in production, stabilization and structural analysis techniques of membrane proteins. This field has made significant advances since the elucidation of the first 3-D structure of a recombinant G Protein Coupled Receptor (GPCR), rhodopsin, with the structure of several more GPCRs having been solved in the past five years. In fact, the 2012 Nobel Prize in Chemistry was awarded for groundbreaking discoveries on the inner workings of GPCRs. This book is essential reading for all researchers, biochemists and crystallographers working with membrane proteins, who are interested by the structural characterization of their favorite protein and who wish to follow the expression, migration, modifications and recycling of a membrane protein.

Each review within the volume critically surveys one aspect of that topic and places it within the context of the volume as a whole. The most significant developments of the last 5 to 10 years are presented using selected examples to illustrate the principles discussed. The coverage is not intended to be an exhaustive summary of the field or include large quantities of data, but should rather be conceptual, concentrating on the methodological thinking that will allow the non-specialist reader to understand the information presented. Contributions also offer an outlook on potential future developments in the field.