Glycosyltransferases (GTs) are essential for the biosynthesis of complex glycoconjugates and are powerful tools to study the functions of complex glycans in health, development and disease. Complex glycoconjugates, such as glycoproteins, proteoglycans and glycolipids, are assembled by GTs which synthesize specific linkages between sugars or sugars and protein. This is in contrast to the non-specific or less specific chemical glycation reactions, transglycosylation and reverse glycosylation reactions. Glycosyltransferases: Methods and Protocols contains a wide range of studies, methods and protocols which form a solid basis for investigations of the role and mechanisms, biology and pathology involving GTs. Written in the successful Methods in Molecular Biology (TM) 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, Glycosyltransferases: Methods and Protocols is a vital contribution to glycobiology and glycopathology, and to applications of these enzymes in biotechnology and drug development. It will prove invaluable to students, postdoctoral fellows, and senior scientists carrying on research of GTs that has been intensified over the last years.

This book aims to bridge the gap in understanding how protein-tyrosine phosphatases (PTPs), which carry out the reverse reaction of tyrosine phosphorylation, feature in cancer cell biology. The expertly authored chapters will first review the general features of the PTP superfamily, including their overall structure and enzymological properties; use selected examples of individual PTP superfamily members, to illustrate emerging data on the role of PTPs in cancer; and will review the current status of PTP-based drug development efforts. Protein Tyrosine Phosphatases in Cancer,from renowned researchers Benjamin Neel and Nicholas Tonks, is invaluable reading for researchers in oncology, stem cell signaling,and biochemistry.

This comprehensive volume completes Frederic Holmes's notable and detailed biography of Hans Krebs, from the investigator's early development through the major phase of his groundbreaking investigation, which lay the foundations upon which the modern structure of intermediary metabolism is built. With access to Krebs's research notebooks as well as to Krebs himself through more than five years of personal interviews, the author provides an insightful analysis of Hans Krebs and of the scientific process as a whole. The first volume, published in 1991, covered Krebs's formative years in Germany, his work with Otto Warburg, and his discovery of the urea cycle in 1932. This second volume reconstructs the investigative pathway and the professional and personal life of Hans Krebs, from the time of his arrival in England in 1933 until 1937, when he made the discovery for which he is best known-the formulation of the citric acid cycle. Holmes portrays Krebs's activity at the intimate level of daily interactions of thought and action, from which the characteristic patterns of scientific creativity can best be seen. Holmes's fascinating portrait of Krebs integrates the great scientist's investigative pathways with his personal life. The result is an illuminating analysis of both man and scientist that will be of interest to biochemists and historians of science.

This volume arranged into three sections describes biochemical, in vitro, and in vivo protocols on Semaphorins. Chapters focus on approaches that would allow the novice to study Semaphorins and employ robust assays to characterize mechanisms of action. 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, Semaphorin Signaling: Methods and Protocols aims to ensure successful results in the further study of this vital field.

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.

Super secondary structure(SSS) helps to understand the relationship between primary and tertiary structure of proteins. In Protein Supersecondary Structure: Methods and Protocols expert researchers in the field detail the usefulness of the study of super secondary structure in different areas of protein research. This is done through four main studies SSS representation, SSS prediction, SSS and protein folding, and other application of SSS concept to protein biology. Written in the highly successful Methods in Molecular Biology (TM) 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, Protein Supersecondary Structure: Methods and Protocols highlight some of the major advances in the many fast-growing areas of supersecondary structure research.

Rab GTPases now comprise a family of >63 members. They are emerging as the key hub element controlling the membrane architecture of eukaryotic cells. They are intimately involved in vesicle targeting and fusion in both the endocytic and exocytic pathways and direct the assembly and disassembly of protein complexes that include regulators (GEFs and GAPs), effectors (tethers/motors) and fusion components (SNAREs) that control membrane targeting and fusion. During the last 3 years the field has virtually exploded with the identification and characterization of many new Rab proteins and their effectors.
Our understanding of how Rab GTPases control membrane function remains at its infancy. This volume of MIE provides a wealth of new concepts, approaches and tools to study Rab proteins in the test tube and in living cells that will be of strong benefit to both established laboratories and new investigators in the field to elucidate Rab GTPase function in cellular development, differentiation and proliferation.
* Comprehensive overview of Rab GTPase phylogeny and systems biology
* Identification and characterization of Rab GEFs, GAPs and effectors
* General methodologies to study Rab GTPase function in vitro and in vivo using biochemical, molecular and microscopy approaches

This volume on conjugation enzymes and transporters serves to bring together current methods and concepts in an interesting, important and rapidly developing field of cell and systems biology. It focuses on the so-called Phase II enzymes of drug metabolism (xenobiotics), which has important ramifications for endogenous metabolism and nutrition. Also included are aspects on Phase III, transport systems. This volume of Methods in Enzymology presents current knowledge and methodology on glucuronidation, sulfation, acetylation, and transport systems in this field of research. Together with the volumes on Quinones and Quinone Enzymes (volumes 378 and 382), and on Glutathione Transferases and gamma-Glutamyl Transpeptidases (volume 401), the state of knowledge on proteomics and metabolomics of many pathways of (waste) product elimination, enzyme protein induction and gene regulation and feedback control is provided. This volume will help stimulate future investigations and speed the advance of knowledge in systems biology.
*A laboratory standard for more than 40 years
*Over 400 volumes strong
*Also available on ScienceDirect

Volume 45 of Advances in Enzyme Regulation is the proceedings of the 45th International Synthesis in Normal and Neoplastic Tissues held at Indiana University School of Medicine Indianapolis, Indiana September 27-28, 2004.
Volume 45 concentrates on subjects which have reached the stage of productive summarizaiton and critical evaluation in the light of extensive new results. This book also lives up to its goal of advancing a few steps ahead of the general front of mammalian enzymic and metabolic regulation studies.
*Latest information about mammalian enzymic and metabolic regulation studies
*Comprehensive lab resource and teaching companion
*International contributors from academia and industry

DNA (sometimes referred to as the molecule of life), is the most interesting and most important of all molecules. Electrochemistry of Nucleic Acids and Proteins: Towards Electrochemical Sensors for Genomics and Proteomics is devoted to the electrochemistry of DNA and RNA and to the development of sensors for detecting DNA damage and DNA hybridization. Volume 1, in the brand new series Perspectives in Bioanalysis, looks at the electroanalytical chemistry of nucleic acids and proteins, development of electrochemical sensors and their application in biomedicine and in the new fields of genomics and proteomics. The authors have expertly formatted the information for a wide variety of readers, including new developments that will inspire students and young scientists to create new tools for science and medicine in the 21st century.
* Covers highly sophisticated methods of electrochemical analysis of nucleic acids and proteins
* Summarises the present state of electrochemical analysis of nucleic acids and proteins
* Includes future trends in the electrochemical analysis in genomics and proteomics

Real-time PCR (RT-PCR) technology is highly flexible and many alternative instruments and fluorescent probe systems have been developed recently. The decreased hands-on time, increased reliability, and improved quantitative accuracy of RT-PCR methods have contributed to the adoption of RT-PCR for a wide range of new applications. This essential manual presents a comprehensive guide to the most up-to-date technologies and applications, as well as providing an overview of the theory of this increasingly important technique. Renowned experts in the field describe and discuss the latest PCR platforms, fluorescent chemistries, validation software, data analysis, and internal and external controls. This timely and authoritative volume also discusses a wide range of RT-PCR applications including clinical diagnostics, biodefense, RNA expression studies, validation of array data, mutation detection, food authenticity and legislation, NASBA, molecular halotyping, and much more. Real-Time PCR: Current Technology and Applications will be an essential book for all laboratories using PCR.

Proteomics and peptidomics is the detailed understanding of the role that proteins and peptides play in health and disease and is a necessary compliment to genetic analysis. The functional expression analysis of both proteins and peptides plays a central role in modern drug discovery as well as drug development, and is also a key research area in systems biology. Proteomics and Peptidomics captures the width as well as the depth within the area and exemplifies the variety as well as the traditional basis of analytical chemistry that is needed in order to move forward in expression analysis studies. As a fast emerging field, it gives and overview of parts within the field combined with highly specialized and dedicated topics that are intended to compliment each other.

The critically acclaimed laboratory standard, Methods in Enzymology, is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. The series contains much material still relevant today - truly an essential publication for researchers in all fields of life sciences.
Molecular Evolution Producing the Biochemical Data part B is a continuation of methods published in Part A (1993, volume 224). The work is a very methodological look at markers, templates, genomes, datasets and analyses used in studies of biological diversity.
* One of the most highly respected publications in the field of biochemistry since 1955
* Frequently consulted, and praised by researchers and reviewers alike
* Truly an essential publication for anyone in any field of the life sciences

Advances in Insect Physiology publishes eclectic volumes containing important, comprehensive and in-depth reviews on all aspects of insect physiology. It is an essential reference source for invertebrate physiologists and neurobiologists, entomologists, zoologists and insect biochemists. First published in 1963, the serial is now edited by Steve Simpson (Oxford University, UK).

Bioethanol has been recognized as a potential alternative to petroleum-derived transportation fuels. Even if cellulosic biomass is less expensive than corn and sugarcane, the higher costs for its conversion make the near-term price of cellulosic ethanol higher than that of corn ethanol and even more than that of sugarcane ethanol. Conventional process for bioethanol production from lignocellulose includes a chemical/physical pre-treatment of lignocellulose for lignin removal, mostly based on auto hydrolysis and acid hydrolysis, followed by saccharification of the free accessible cellulose portions of the biomass. The highest yields of fermentable sugars from cellulose portion are achieved by means of enzymatic hydrolysis, currently carried out using a mix of cellulases from the fungus Trichoderma reesei. Reduction of (hemi)cellulases production costs is strongly required to increase competitiveness of second generation bioethanol production. The final step is the fermentation of sugars obtained from saccharification, typically performed by the yeast Saccharomyces cerevisiae. The current process is optimized for 6-carbon sugars fermentation, since most of yeasts cannot ferment 5-carbon sugars. Thus, research is aimed at exploring new engineered yeasts abilities to co-ferment 5- and 6-carbon sugars. Among the main routes to advance cellulosic ethanol, consolidate bio-processing, namely direct conversion of biomass into ethanol by a genetically modified microbes, holds tremendous potential to reduce ethanol production costs. Finally, the use of all the components of lignocellulose to produce a large spectra of biobased products is another challenge for further improving competitiveness of second generation bioethanol production, developing a biorefinery.

In Viral Membrane Proteins Structure, Function, and Drug Design, Wolfgang Fischer summarizes the current structural and functional knowledge of membrane proteins encoded by viruses. In addition, contributors to the book address questions about proteins as potential drug targets. The range of information covered includes signal proteins, ion channels, and fusion proteins.

This book has a place in the libraries of researchers and scientists in a wide array of fields, including protein chemistry, molecular biophysics, pharmaceutical science and research, bioanotechnology, molecular biology, and biochemistry.

This volume of Modern Aspects of Electrochemistry reviews the latest developments in electrochemical science and technology related to biomedical and pharmaceutical applications. In particular, this book discusses electrochemical applications to medical devices, implants, antimicrobially active materials, and drug delivery systems.

Fibrous Protein: Coiled-Coils, Collagen and Elastomers is the first of a three-part series on Fibrous Proteins. The books are based on a very successful workshop in Alpbach, Austria on the general topic of Fibrous Proteins that gave rise to the award winning issue of Journal of Structural Biology. Part II will contain an extensive discussion of Molecular Motors and Muscle, Part III on Amyloids, Prions and Beta Proteins.
Advances in Protein Chemistry is available online on ScienceDirect full-text online of volumes 53 onwards.
*Reveals new structural and functional aspects of fibrous proteins
*Based on Fibrous Protein workshop in Alpbach, Austria that gave rise to 2003 Nobel Prize winners in Chemistry

The volume focuses on the genomics, proteomics, metabolomics, and bioinformatics of a single cell, especially lymphocytes and on understanding the molecular mechanisms of systems immunology. Based on the author's personal experience, it provides revealing insights into the potential applications, significance, workflow, comparison, future perspectives and challenges of single-cell sequencing for identifying and developing disease-specific biomarkers in order to understand the biological function, activation and dysfunction of single cells and lymphocytes and to explore their functional roles and responses to therapies. It also provides detailed information on individual subgroups of lymphocytes, including cell characters, function, surface markers, receptor function, intracellular signals and pathways, production of inflammatory mediators, nuclear receptors and factors, omics, sequencing, disease-specific biomarkers, bioinformatics, networks and dynamic networks, their role in disease and future prospects. Dr. Xiangdong Wang is a Professor of Medicine, Director of Shanghai Institute of Clinical Bioinformatics, Director of Fudan University Center for Clinical Bioinformatics, Director of the Biomedical Research Center of Zhongshan Hospital, Deputy Director of Shanghai Respiratory Research Institute, Shanghai, China.

TheobservationthatabloodclotspontaneouslydissolveswasfirstdescribedbyDenys in1889. Subsequently,thebloodclottingsystemwasshowntobeinvolvedintumor growth. Forexample,asearlyas1925,Fisherreportedthataviantissueexplantstrans- formedtomalignancybyvirusesgeneratedhighlevelsoffibrinolyticactivityundercon- ditionsinwhichculturesofnormalcellsdidnot. In1958,theconceptthatan equilibriumexistedbetweenthetendencyofbloodtoclotandtoremainfluidwaspro- posedbyAstrup. Atthattime,itwasbelievedthatthishemostaticbalancewasexplained bytheabilityofpolymerizingfibrintoorchestrateitsownclearancebystimulatingfib- rinolyticactivity. Sincethesepioneeringstudies,considerableinformationhasaccumu- latedthathasdefinedthecomponentsofthecoagulationandfibrinolyticsystemsand howtheyareinvolvedinphysiologicalandpathophysiologicalprocesses. Plasminogen: Structure, activation, and regulationfocusesonthebasicprinciplesandrecentdevelop- mentsintheplasminogen/plasminresearchfieldandhowtheseresultsprovideacon- ceptualframeworkforanunderstandingofthephysiologicalroleofplasminogenin healthanddisease. Theenzymaticcascadetriggeredbyactivationofplasminogenhasbeenimplicated inavarietyofnormalandpathologicaleventssuchasfibrinolysis,woundhealing,tis- sueremodeling,embryogenesis,angiogenesis,andtheinvasionandmetastasisoftumor cells. Thisimpressivelistofphysiologicalfunctionsforplasminogenreinforcesthewide diversityofrolesthatplasminogenplaysinvariousphysiologicalprocesses. Productive plasmingenerationrequirestheassemblyofbothplasminogenactivatorsandplasmino- genonasolidsupportsuchasthefibrinpolymerorthecellsurface. Theregulationof plasminproductioninvolvesacomplexinterplaybetweentheseplasminogenactivators, plasminogenactivatorinhibitors,andplasmininhibitors. Clearly,theexplosivegrowth inthisresearchfieldandthemanyexcitingdiscoveriessuggeststhattheresearchefforts inthenextdecadewillrevealthemechanismsbywhichthecomponentsoftheplas- minogensysteminteractandregulatebothplasminactivationandfunctionatacellular level. Plasminogen: Structure, activation, and regulationisdividedintotwosections. Thefirstsectiondealswiththestructureandregulationofplasminogen. Thechapters inthissectionrangefromdiscussionsofthestructureofplasminogenandtheregulation oftheplasminogengenetodiscussionsofthestructureandregulationofplasminogen activatorsandplasminogenactivatorinhibitors. Alsoexaminedistherelativelynewdata concerningthegenerationofanti-angiogenicmoleculesfromplasminogen. Thesecond sectiondealswiththephysiologicalandpathophysiologicalrolesofplasminogenaswell astheconsequencesofplasminogengeneknockout. Discussionsinthissectioninclude examinationoftheroleofplasminogeninhematopoieticmalignancies,tumorcell progression,angiogenesis,mammaryglandinvolution,woundhealing,andbone readsorption. xi xii Preface Inclosing,Iwouldliketothankmyadministrativeassistant,Ms. ViSommerfeld,for herinvaluableassistanceandtimelesseffortswiththeorganizationandeditingofthebook. Lastly,Iwouldliketoacknowledgetheeffortsoftheauthorsoftheindividualchapters, whoareauthorities inthisfield,foragreeingtotaketimefrombusyschedulestoprovide thesechaptersinatimelyfashion. DavidMortonWaisman Contents Part I. Plasminogen: Structure and Regulation 1. Human Plasminogen: Structure, Activation, and Function FrancisJ. Castellino and Victoria A. Ploplis 1. Introduction 3 2. StructureofHumanPlasminogen...3 2. 1. PrimaryProteinStructure...3 2. 2. GeneOrganization 5 3. ActivationofHumanPlasminogen...6 3. 1. ActivationbyPhysiologicalActivators 7 3. 1. 1. Urokinase-typePlasminogenActivator...7 3. 1. 2. Tissue-typePlasminogenActivator...8 3. 2. ActivationbyBacterial-derivedPlasminogenActivators...9 3. 2. 1. Streptokinase 9 3. 2. 2. Staphylokinase...9 4. TargetsforPlasminActivity...9 5. DysplasminogenemiasandPhenotypicManifestations 10 6. Conclusions 11 References...11 2. Plasminogen Activators: Structure and Function Vincent Ellis 1. Introduction ...19 2. SerineProteases...20 3. UrokinasePlasminogenActivator,uPA...21 3. 1. SerineProteaseDomain 22 3. 2. N-terminalDomains...24 3. 2. 1. KRModule 24 3. 2. 2. EGModule 24 4. MechanismsRegulatinguPAFunction...25 4. 1. ZymogenActivation...25 4. 2. ZymogenActivity...26 4. 3. ReciprocalZymogenActivation 27 4. 4. uPARStimulationofPlasminogenActivation...27 4. 4. 1. uPAandtheTemplateMechanism 28 4. 4. 2. PlasminogenandtheTemplateMechanism 29 4. 5. AvianuPA,aSpecialCase? 30 xiii xiv Contents 5. TissuePlasminogenActivator,tPA...30 5. 1. SerineProteaseDomain 31 5. 2. N-terminalDomains ,...33 5. 2. 1. KRModules ,. . ,. . ,...33 5. 2. 2. F1-EGSupermodule 33 6.

Food Toxicants Analysis covers different aspects from the field of analytical food toxicology including emerging analytical techniques and applications to detect food allergens, genetically modified organisms, and novel ingredients (including those of functional foods). Focus will be on natural toxins in food plants and animals, cancer modulating substances, microbial toxins in foods (algal, fungal, and bacterial) and all groups of contaminants (i.e., pesticides), persistent organic pollutants, metals, packaging materials, hormones and animal drug residues. The first section describes the current status of the regulatory framework, including the key principles of the EU food law, food safety, and the main mechanisms of enforcement. The second section addresses validation and quality assurance in food toxicants analysis and comprises a general discussion on the use of risk analysis in establishing priorities, the selection and quality control of available analytical techniques. The third section addresses new issues in food toxicant analysis including food allergens and genetically modified organisms (GMOs). The fourth section covers the analysis of organic food toxicants.
* step-by-step guide to the use of food analysis techniques
* eighteen chapters covering emerging fields in food toxicants analysis
* assesses the latest techniques in the field of inorganic analysis

The proposed volume provides both fundamental and detailed information about the computational and computational-experimental studies which improve our knowledge of how leaving matter functions, the different properties of drugs (including the calculation and the design of new ones), and the creation of completely new ways of treating numerical diseases. Whenever it is possible, the interplay between theory and experiment is provided. The book features computational techniques such as quantum-chemical and molecular dynamic approaches and quantitative structure-activity relationships. The initial chapters describe the state-of-the art research on the computational investigations in molecular biology, molecular pharmacy, and molecular medicine performed with the use of pure quantum-chemical techniques. The central part of the book illustrates the status of computational techniques that utilize hybrid, so called QM/MM approximations as well as the results of the QSAR studies which now are the most popular in predicting drugs' efficiency. The last chapters describe combined computational and experimental investigations.

Liposomes are cellular structures made up of lipid molecules. Important as a cellular model in the study of basic biology, liposomes are also used in clinical applications such as drug delivery and virus studies. Liposomes Part E is a continuation of previous MIE Liposome volumes A, B, C and D.
* One of the most highly respected publications in the field of biochemistry since 1955
* Frequently consulted, and praised by researchers and reviewers alike
* Truly an essential publication for anyone in any field of the life sciences