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The zinc metalloproteases are a diverse group of enzymes which are becoming increasingly important in a variety of biological systems. Their major function is to break down proteins. This text presents recent research results on the biochemistry and molecular biology of these enzymes.
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 members of an enzyme family and are critical for maintaining tissue allostasis. MMPs can catalyze normal turnover of the extracellular matrix (ECM) together with other metalloproteinases such as ADAM (a disintegrin and metalloproteinase) and ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) families. MMP activity is also regulated by a group of endogenous proteins called tissue inhibitor of metalloproteinases (TIMPs). All these proteins have a pivotal role involving ECM remodelling in normal physiological processes such as wound healing, embryogenesis, angiogenesis, bone remodelling, immunity, and the female reproductive cycle. An imbalance in the expression or activity of MMPs can also have important consequences in diseases such as cancer, cardiovascular disease, peripheral vascular disease, chronic leg ulcers, and multiple sclerosis. In recent years, MMPs have been found to play an important role in the field of precision medicine, as they may serve as biomarkers that may predict an individual's disease predisposition, state, or progression. MMPs are also thought to be a sensible target for molecular therapy. The aim of this Special Issue is to explore the most recent findings in this field that may have an impact in healthcare systems.
Over the last decades cell biology and biological chemistry have increasingly turned their attention to the space between cells and revealed an elaborate network of macromolecules essential for structural support, cell adhesion and signaling. This comprehensive handbook of the extracellular matrix will give an overview of the current state of knowledge of matrix components (structure and function), their role in heath and disease (matrix pathobiology) and new aspects related to pharmacological targeting. It will provide an introduction to the extracellular matrix and detailed sections and chapters on: Importance of extracellular matrix in health and disease Matrix proteoglycans (aggrecan, versican, perlecan, SLRPs, syndecans, glypicans, serglycin) Matrix proteinases (remodeling, would healing, regulatory roles in health and disease, metalloproteinases, cystein proteases, plasmin and plasminogen activator system) Glycobiology (hyaluronan and sulfated glycosaminoglycans in cancer, inflammation and metabolic control) Collagens (supramolecular assembly, proteins binding collagen, scaffolds, bacterial and mutated collagens, procollagen proteinases) Cell surface receptors (integrins, syndecans, mechanical strain and TGFb, CD44 and DDR). Biotechnological and pharmacological outlook (matrix regulation by growth factors, hyaluronidases, pathobiology, disease targeting, delivery systems, EMT and proteomics). "The book Extracellular Matrix: Pathobiology and Signaling provides a comprehensive and up to date collection of very relevant topics for understanding the various facets of extracellular matrix and its interactions with cells in normal tissue as well as in disease. It represents the current front-line and will serve as a reference for extracellular matrix and posttranslational modifications." Dick Heinegård, Department of Clinical Sciences Lund, Section Rheumatology, Lund University, Sweden
This volume of Current Topics in Membranes focuses on metal transmembrane transporters and pumps, a recently discovered family of membrane proteins with many important roles in the physiology of living organisms. The book summarizes the most recent advances in the field of metal ion transport and provides a broad overview of the major classes of transporters involved in homeostasis of heavy metals. Various families of the transporters and metal specificities are discussed with the focus on the structural and mechanistic aspects of their function and regulation. The reader will access information obtained through a variety of approaches ranging from X-ray crystallography to cell biology and bioinformatics, which have been applied to transporters identified in diverse biological systems, such as pathogenic bacteria, plants, humans and others. Field is cutting-edge and a lot of the information is new to research community Wide breadth of topic coverage Contributors of high renown and expertise
We present to our readers the proceedings of the Second International Workshop on Phosphate. A short account of the history of the effort led to the Phosphate Workshops is appro priate and can be of interest to the reader. The idea for Phosphate Workshops was born in the early days of November, 1974. One of us (S. G. M. ) suggested the thought to a group of scientists gathered for a luncheon in one of the attrac tive small restaurants in Weisbaden, Germany. The purpose of the workshop was to bring together interested scientists to discuss the newer developments and the recent advances in the field of phosphate metabolism and the other related minerals. An Organizing Committee made of Shaul G. Massry (USA), Louis V. Avioli (USA), Philippe Bordier (France), Herbert Fleisch (Switzerland), and Eduardo Slatopolsky (USA) was formed. The First Workshop was held in Paris during June 5-6, 1975 and was hosted by Dr. Philippe Bordier. Its proceeding was already published. The Second Workshop took place in Heidelberg during June 28-30, 1976 and was hosted by Dr. Eberhard Ritz. Both of these workshops were extremely successful scientific endeavors, and the need for them was demonstrated by the great interest they generated among the scientific community. The Or ganizing Committee, therefore, decided to continue with the tradi tion to hold additional Workshops annually or every other year.
Cutting-edge investigators review the current status of the entire field, from the biology of MMPs through the current clinical studies. The authors include many leading scientists from pharmaceutical companies who present all the latest concepts and results on the preferred design strategies for MMP inhibitors, their molecular mechanisms, and their substrates. In addition, they fully describe their personal research on specific MMP inhibitors, detailing vanguard design strategies, their in vitro activity, the outcome of animal model studies and, where available, their toxicology, safety, efficacy in human clinical trials. Comprehensive and state-of-the-art, Matrix Metalloproteinase Inhibitors in Cancer Therapy offers basic and clinical investigators alike a richly informative summary of all the latest research on these powerful new drugs, and their high promise as emerging cancer therapeutics.
This book is a printed edition of the Special Issue "Snake Venom Metalloproteinases" that was published in Toxins
Gangliosides in Health and Disease, Volume 156, presents the latest information on Gangliosides, a class of glycolipids that are found on all vertebrate cell surfaces, and are particularly abundant in the brain. Individual chapters in this new volume cover Gangliosides as Toxin Receptors, Gangliosides in Cancer Cell Signaling, Gangliosides in inflammation and neurodegeneration, Gangliosides as functional galectin receptors, Gangliosides in signal transduction, Gangliosides in brain tumor immunology, and Gangliosides in axon regeneration and stability, amongst other related topics. This book brings together world experts in ganglioside structure and function who have been assembled to contribute to this thorough update of the field. Contains accessible content that is ideal for students and researchers alike Written by leading authorities in the field
In the ten-year interval since the first edition of this volume went to press, our knowledge of extracellular matrix (ECM) function and structure has enor mously increased. Extracellular matrix and cell-matrix interaction are now routine topics in the meetings and annual reviews sponsored by cell biology societies. Research in molecular biology has so advanced the number of known matrix molecules and the topic of gene structure and regulation that we won dered how best to incorporate the new material. For example, we deliberated over the inclusion of chapters on molecular genetics. We decided that with judicious editing we could present the recent findings in molecular biology within the same cell biology framework that was used for the first edition, using three broad headings: what is extracellular matrix, how is it made, and what does it do for cells? Maintaining control over the review of literature on the subject of ECM was not always an easy task, but we felt it was essential to production of a highly readable volume, one compact enough to serve the the student as an introduction and the investigator as a quick update on graduate the important recent discoveries. The first edition of this volume enjoyed con hope the reader finds this edition equally useful. siderable success; we D. Hay Elizabeth vii Contents Introductory Remarks 1 Elizabeth D. Hay PART I. WHAT IS EXTRACELLULAR MATRIX? Chapter 1 Collagen T. F. Linsenmayer 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2. The Collagen Molecule . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2. 1. Triple-Helical Domain(s) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .