This study covers the sequence information, three-dimensional structures, activation, protein substrates, specificity requirements, inhibition, and biological roles of identified MMPs.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in many physiological and pathological processes. The field of MMP research is very important due to the implications of the distinct paralogs in both human physiology and pathology. Over-activation of these enzymes results in tissue degradation, producing a wide array of disease processes such as rheumatoid arthritis, osteoarthritis, tumor growth and metastasis, multiple sclerosis, congestive heart failure, and others. Thus MMP inhibitors are candidates for therapeutic agents to combat a number of diseases. The present book discusses the design and development of different classes of inhibitors of important classes of MMPs, such as gelatinases and collagenases. The articles focus specifically on structure-activity relationships of all classes of compounds and on their modes of action and specificity of binding with the receptors based on experimental and theoretical studies. These studies constitute a valuable asset for all those involved in drug development.

Discussing recent advances in the field of matrix metalloproteinase (MMP) research from a multidisciplinary perspective, Matrix Metalloproteinase Biologyis a collection of chapters written by leaders in the field of MMPs. The book focuses on the challenges of understanding the mechanisms substrate degradation by MMPs, as well as how these enzymes are able to degrade large, highly ordered substrates such as collagen. All topics addressed are considered in relation to disease progression including roles in cancer metastasis, rheumatoid arthritis and other inflammatory diseases. The text first provides an overview of MMPs, focusing on the history, the development and failures of small molecule inhibitors in clinical trials, and work with TIMPS, the endogenous inhibitors of MMPs. These introductory chapters establish the foundation for later discussion of the recent progress on the design of different types of inhibitors, including novel antibody based therapeutics. The following section emphasizes research using novel methods to further the study of the MMPs. The third and final section focuses on in vivo research, particularly with respect to cancer models, degradation of the extracellular matrix, and MMP involvement in other disease states. Written and edited by leaders in the field, Matrix Metalloproteinase Biology addresses the rapidly growth in MMP research, and will be an invaluable resource to advanced students and researchers studying cell and molecular biology.

The chapters in this book thoroughly cover the structure, regulation, and function of matrix metalloproteinases, and provide information on the latest strategies to inhibit enzyme activity. This work will be an indispensable reference tool for investigators with an interest in extracellular matrix biology, matrix turnover, enzymology and biochemistry of proteinases, developmental biology, pathology, and therapeutic interventions. Provides state-of-the-art information on a field with broad implications to many areas of biology Includes detailed coverage of the structure and regulation of all major matrix metalloproteinases Chapters focus on a timely and expanding field Topics have direct relevance to understanding human disease pathology of cancer, arthritis, and vascular disease Discusses latest strategies used in the development of new therapeutics to inhibit metalloproteinase activity

The biochemistry and cell biology of Matrix Metalloproteinases (MMPs) are not necessarily straightforward, but basic information on the history of these enzymes, their various functions that extend far beyond the cleaving of the extracellular matrix, and the complex mechanisms that control their expression are valuable to both scientists and clinicians. This volume summarizes the salient features and functions of MMPs and applies this information in a practical manner in order to understand how they contribute to normal physiology and pathology of selected diseases. Chapters by noted clinicians Jean-Michel Dayer, MD in rheumatology, Jian Cao, MD in oncology, and Peter Libby, MD in cardiology, represent important practical and clinically-oriented contributions.

Matrix Metalloproteinases and Tissue Remodeling in Health and Disease: Cardiovascular Remodeling, Volume 147 contains up-to-date information on the biology and function of matrix metalloproteinases and how their effects on tissue remodeling are altered in diseases of the cardiovascular, pulmonary, and musculoskeletal systems and in other tissues and organs, and in cancer. This latest release covers such highly evolving topics as Biochemical and Biological Attributes of Matrix Metalloproteinases, Matrix Metalloproteinases in Myocardial Infarction and Heart Failure, The Balance Between Metalloproteinases and TIMPs: Critical Regulator of Microvascular Endothelial Cell Function in Health and Disease, and Matrix Metalloproteinases and Platelet Function. As part of the Progress in Molecular Biology and Translational Science, users will find contributions from prominent scientists and highly-recognized experts who have major accomplishments in the research field of matrix metalloproteinases. Focuses on matrix metalloproteinases and their role in tissue remodeling under physiological and pathological conditions Contains up-to-date information on matrix metalloproteinases that is clearly presented in a concise fashion with helpful illustrations and supporting references Includes comprehensive reviews written by prominent scientists and highly-recognized experts in the field of matrix metalloproteinases and tissue remodeling

Research in the matrix metalloproteinase field began with the demonstration by Gross and Lapière, in 1962, that resorbing tadpole tail expressed an enzyme that could degrade collagen gels. These humble beginnings have led us to the elucidation of around twenty distinct vertebrate MMPs, along with a variety of homologs from such diverse organisms as sea urchin, plants, nematode worm, and bacteria. This, coupled with four known specific inhibitors of MMPs, the TIMPs, gives a complex picture. Part I of Matrix Metalloproteinase Protocols provides the reader with a selective overview of the MMP arena, and a chance to come to grips with where the field has been, where it is, and where it is going. I hope that this complements all of the methodology that comes later. Part II presents the reader with a diverse set of methods for the expression and purification of MMPs and TIMPs, bringing together the long and often hard-earned experience of a number of researchers. Part III allows the reader to detect MMPs and TIMPs at both the protein and mRNA level, whereas Part IV gives the ability to assay MMP and TIMP activities in a wide variety of circumstances.