Proteases in Health and Disease

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ISBN: 9780123855046 | 0123855047
Cover: Hardcover
Copyright: 1/24/2011

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Proteases occur naturally in all organisms. They are enzymes which 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

Contributors	p. ix
Preface	p. xi
Membrane-Anchored Serine Proteases in Health and Disease	p. 1
Introduction	p. 2
Structural Features	p. 4
Regulation by Endogenous Inhibitors	p. 7
The Type I Transmembrane Serine Protease	p. 7
The Type II Transmembrane Serine Proteases	p. 8
The GPI-Anchored Serine Proteases	p. 30
Perspectives	p. 33
References	p. 34
Complex Assemblies of Factors IX and X Regulate the Initiation, Maintenance, and Shutdown of Blood Coagulation	p. 51
Introduction	p. 52
Proteolytic Activation of Trypsin-Like Serine Proteases	p. 54
Low-Molecular Weight Cofactors	p. 61
Protein Cofactors	p. 68
Membranes: Nonhumoral Cofactors of Coagulation Factors	p. 79
Protein Inhibitors of Coagulation Factors	p. 81
Pharmaceutical Opportunities and Challenges	p. 90
Referenes	p. 92
Structure and Proteolytic Properties of ADAMTS13, A Metalloprotease Involved in the Pathogenesis of Thrombotic Microangiopathies	p. 105
Introduction	p. 106
Gene, Biosynthesis and Secretion of ADAMTS13	p. 109
ADAMTS13 Structure and Function: General Aspects	p. 109
ADAMTS13: A Multidomain Enzyme	p. 111
Regulation of ADAMTS13 Activity	p. 118
ADAMTS13 and Its Role in the Pathogenesis of Thrombotic Microangiopathy, A Pleiomorphic Clinical Setting	p. 120
Are ADAMTS13 Changes Always Associated with Thrombotic Microangiopathies?	p. 132
Issues Concerning Laboratory Methods Used to Measure the ADAMTS13 Activity in Clinical Samples	p. 133
Future Directions	p. 134
References	p. 134
Thrombin as an Anticoagulant	p. 145
Preamble	p. 146
Thrombin Interactions	p. 147
Thrombin Structure	p. 148
Thrombin is an Allosteric Enzyme	p. 151
Structures of E°, E, and E:Na⁺	p. 153
Dissociating Procoagulant and Anticoagulant Activities	p. 158
WE: A Prototypic Anticoagulant Thrombin	p. 163
Molecular Mechanism of Anticoagulant Activity of Thrombin Mutants	p. 165
Beyond WE	p. 170
Conclusions	p. 175
References	p. 175
Regulation of Proteases by Protein Inhibitors of the Serpin Superfamily	p. 185
Overview of the Serpin Superfamily	p. 186
Mechanism of Action	p. 197
Rates of Reaction, Specificity, and Regulation	p. 211
Engineering Serpins as Therapeutics	p. 221
Concluding Remarks	p. 230
References	p. 231
Multiple Roles of Metalloproteinases in Neurological Disorders	p. 241
Introduction	p. 242
Biology of Matrix Metalloproteinases	p. 243
MMPs in Neuroinflammation	p. 247
Tissue Inhibitors of Metalloproteinases and Apoptosis	p. 248
The Neurovascular Unit, Tight Junction Proteins, and MMPs	p. 250
MMPs and Cell Death	p. 251
Neurological Disorders	p. 253
Conclusions	p. 257
References	p. 259
Regulation of Caspases in the Nervous System: Implications for Functions in Health and Disease	p. 265
The Caspase Family of Death Proteases	p. 266
Caspases and Developmental Neuronal Death	p. 275
Nonapoptotic Caspase Function in the Nervous System	p. 276
Caspase Function in Neurodegenerative Diseases	p. 277
Future Directions	p. 292
References	p. 292
Index	p. 307
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Proteases in Health and Disease

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