Di Cera Proteases in Health and Disease

1. Auflage 2011
ISBN: 978-0-12-385505-3
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band Volume 99, 328 Seiten, Web PDF

Reihe: Progress in Molecular Biology and Translational Science

Proteases occur naturally in all organisms. They are enzymes that are involved in many physiological reactions such as digestion of food and blood clotting. This volume reviews their role in health and disease and presents the latest research and developments. - Discusses new discoveries, approaches, and ideas - Contributions from leading scholars and industry experts - Reference guide for researchers involved in molecular biology and related fields

Autoren/Hrsg.

Di Cera, Enrico

Inhaltsverzeichnis

1;Front Cover;1
2;Progress in Molecular Biology and Translational Science: Proteases in Health and Disease;4
3;Copyright Page;5
4;Contents;6
5;Contributors;10
6;Preface;12
7;Chapter 1: Membrane-Anchored Serine Proteases in Health and Disease;14
7.1;I. Introduction;15
7.2;II. Structural Features;17
7.3;III. Regulation by Endogenous Inhibitors;20
7.4;IV. The Type I Transmembrane Serine Protease;20
7.5;V. The Type II Transmembrane Serine Proteases;21
7.6;VI. The GPI-Anchored Serine Proteases;43
7.7;VII. Perspectives;46
7.8;Acknowledgments;47
7.9;References;47
8;Chapter 2: Complex Assemblies of Factors IX and X Regulate the Initiation, Maintenance, and Shutdown of Blood Coagulation;64
8.1;I. Introduction;65
8.2;II. Proteolytic Activation of Trypsin-Like Serine Proteases;67
8.3;III. Low-Molecular Weight Cofactors;74
8.4;IV. Protein Cofactors;81
8.5;V. Membranes: Nonhumoral Cofactors of Coagulation Factors;92
8.6;VI. Protein Inhibitors of Coagulation Factors;94
8.7;VII. Pharmaceutical Opportunities and Challenges;103
8.8;Acknowledgments;105
8.9;References;105
9;Chapter 3: Structure and Proteolytic Properties of ADAMTS13, A Metalloprotease Involved in the Pathogenesis of Thrombotic Microangiopathies ;118
9.1;I. Introduction;119
9.2;II. Gene, Biosynthesis and Secretion of ADAMTS13;122
9.3;III. ADAMTS13 Structure and Function: General Aspects;122
9.4;IV. ADAMTS13: A Multidomain Enzyme;124
9.5;V. Regulation of ADAMTS13 Activity;131
9.6;VI. ADAMTS13 and Its Role in the Pathogenesis of Thrombotic Microangiopathy, A Pleiomorphic Clinical Setting;133
9.7;VII. Are ADAMTS13 Changes Always Associated with Thrombotic Microangiopathies?;145
9.8;VIII. Issues Concerning Laboratory Methods Used to Measure the ADAMTS13 Activity in Clinical Samples;146
9.9;IX. Future Directions;147
9.10;References;147
10;Chapter 4: Thrombin as an Anticoagulant;158
10.1;I. Preamble;159
10.2;II. Thrombin Interactions;160
10.3;III. Thrombin Structure;161
10.4;IV. Thrombin is an Allosteric Enzyme;164
10.5;V. Structures of E*, E, and E:Na+;166
10.6;VI. Dissociating Procoagulant and Anticoagulant Activities;171
10.7;VII. WE: A Prototypic Anticoagulant Thrombin;176
10.8;VIII. Molecular Mechanism of Anticoagulant Activity of Thrombin Mutants;178
10.9;IX. Beyond WE;183
10.10;X. Conclusions;188
10.11;Acknowledgments;188
10.12;References;188
11;Chapter 5: Regulation of Proteases by Protein Inhibitors of the Serpin Superfamily;198
11.1;I. Overview of the Serpin Superfamily;199
11.2;II. Mechanism of Action;210
11.3;III. Rates of Reaction, Specificity, and Regulation;224
11.4;IV. Engineering Serpins as Therapeutics ;234
11.5;V. Concluding Remarks;243
11.6;References;244
12;Chapter 6: Multiple Roles of Metalloproteinases in Neurological Disorders;254
12.1;I. Introduction;255
12.2;II. Biology of Matrix Metalloproteinases;256
12.3;III. MMPs in Neuroinflammation;260
12.4;IV. Tissue Inhibitors of Metalloproteinases and Apoptosis;261
12.5;V. The Neurovascular Unit, Tight Junction Proteins, and MMPs;263
12.6;VI. MMPs and Cell Death;264
12.7;VII. Neurological Disorders;266
12.8;VIII. Conclusions;270
12.9;References;272
13;Chapter 7: Regulation of Caspases in the Nervous System: Implications for Functions in Health and Disease;278
13.1;I. The Caspase Family of Death Proteases;279
13.2;II. Caspases and Developmental Neuronal Death;288
13.3;III. Nonapoptotic Caspase Function in the Nervous System ;289
13.4;IV. Caspase Function in Neurodegenerative Diseases;290
13.5;V. Future Directions;305
13.6;References;305
14;Index;320
15;Color Plates;328