Proteases: Structure and Function

1. Front Matter

   Pages i-xii

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2. Protease Families, Evolution and Mechanism of Action

   • Neil D. Rawlings

   Pages 1-36

3. Kinetics of the Interaction of Peptidases with Substrates and Modifiers

   • Antonio Baici, Marko Novinec, Brigita Lenarčič

   Pages 37-84

4. Compartmentalization of Proteolysis

   • Klaudia Brix, Christopher J. Scott, Margarete M. S. Heck

   Pages 85-125

5. Cathepsins: Getting in Shape for Lysosomal Proteolysis

   • Ann H. Erickson, Ciro Isidoro, Lukas Mach, John S. Mort

   Pages 127-173

6. Limited and Degradative Proteolysis in the Context of Posttranslational Regulatory Networks: Current Technical and Conceptional Advances

   • Stefan Tholen, Maria Magdalena Koczorowska, Zon Weng Lai, Joern Dengjel, Oliver Schilling

   Pages 175-216

7. Exploring Systemic Functions of Lysosomal Proteases: The Perspective of Genetically Modified Mouse Models

   • Martina Gansz, Ursula Kern, Christoph Peters, Thomas Reinheckel

   Pages 217-233

8. Astacins: Proteases in Development and Tissue Differentiation

   • Walter Stöcker, F. Xavier Gomis-Rüth

   Pages 235-263

9. Proteases in Death Pathways

   • Andreas Flütsch, Markus G. Grütter

   Pages 265-302

10. ADAM Proteases in Physiology and Pathophysiology: Cleave to Function in Health or to Cause Disease

    • Joachim Grötzinger, Stefan Rose-John

    Pages 303-318

11. Proteases in the Nervous System

    • Holger Cynis, Stefan F. Lichtenthaler, Leona Wagner, Hans-Ulrich Demuth

    Pages 319-371

12. Proteases in the Mammalian Digestive System

    • S. Gaylen Bradley, Toni M. Antalis, Judith S. Bond

    Pages 373-393

13. Calpains in Health and Disease

    • John Anagli, Kevin K. W. Wang, Yasuko Ono, Hiroyuki Sorimachi

    Pages 395-431

14. Metalloproteinases in Cartilage Matrix Breakdown: The Roles in Rheumatoid Arthritis and Osteoarthritis

    • Hideaki Nagase, Gillian Murphy

    Pages 433-469

15. MMP-Mediated Collagen Remodeling and Vessel Functions

    • Agnès Noel, Nor Eddine Sounni

    Pages 471-489

16. Proteases in Cancer: Significance for Invasion and Metastasis

    • Bonnie F. Sloane, Karin List, Barbara Fingleton, Lynn Matrisian

    Pages 491-550

17. Back Matter

    Pages 551-564

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Proteolysis is an irreversible posttranslational modification affecting each and every protein from its biosynthesis to its degradation. Limited proteolysis regulates targeting and activity throughout the lifetime of proteins. Balancing proteolysis is therefore crucial for physiological homeostasis. Control mechanisms include proteolytic maturation of zymogens resulting in active proteases and the shut down of proteolysis by counteracting endogenous protease inhibitors. Beyond the protein level, proteolytic enzymes are involved in key decisions during development that determine life and death – from single cells to adult individuals. In particular, we are becoming aware of the subtle role that proteases play in signaling events within proteolysis networks, in which the enzymes act synergistically and form alliances in a web-like fashion. Proteases come in different flavors. At least five families of mechanistically distinct enzymes and even more inhibitor families are known to date, many family members are still to be studied in detail. We have learned a lot about the diversity of the about 600 proteases in the human genome and begin to understand their physiological roles in the degradome. However, there are still many open questions regarding their actions in pathophysiology. It is in this area where the development of small molecule inhibitors as therapeutic agents is extremely promising. Approaching proteolysis as the most important, irreversible post-translational protein modification essentially requires an integrated effort of complementary research disciplines. In fact, proteolytic enzymes seem as diverse as the scientists working with these intriguing proteins. This book reflects the efforts of many in this exciting field of research where team and network formations are essential to move ahead.

• enzyme
• proteinase
• proteinase function
• proteinase structure
• Protein Structure

• SCHOOL OF ENGINEERING AND SCIENCE, JACOBS UNIVERSITY BREMEN, Bremen, Germany

  Klaudia Brix

• Institute of Zoology, Johannes Gutenberg University Mainz, Mainz, Germany

  Walter Stöcker

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