Chemistry of Proteolysis

by Vladimir K. Antonov

Overview

A first edition of this book appeared in Russian language in 1983. Since those days the interest in proteolytic enzymes has acquired a new impulse due to advances in genetic engineering techniques, which facilitated structural and func­ tional studies of the enzymes. Much more data on a crucial role of proteases in biological processes in norm and pathology are available now. Information that appeared in the past 8 years prompted a renewal of the book and furnishing a supplement especially made for the English edition. The book retains the presentation of the previous edition and yet enlarges the scope to cover the methods for site-directed mutagenesis of amide hydrolases, catalyti­ cally active antibodies, etc. I have tried to preserve the book as a means of reference for the reader. A list of enzymes has been expanded and the biblio­ graphy up to 1990 enlarged by half as much. I am grateful to the translators T. E. Chernichko, N. 1. Loboda and my co­ worker Dr. S. L. Alexandrov for their assistance in the preparation ofthis edition and I feel happy that my book is now available for enzymologists abroad.

Product Details

ISBN-13:	9783662009819
Publisher:	Springer Berlin Heidelberg
Publication date:	11/21/2012
Edition description:	Softcover reprint of the original 1st ed. 1993
Pages:	495
Product dimensions:	6.10(w) x 9.25(h) x 0.04(d)

Table of Contents

1 Substrates.- 1.1 General Characteristics.- 1.2 Amide Group.- 1.3 Unusual (Nonpeptide) Amide Bonds and Other Bonds of Carboxylic Acid Derivatives.- 1.4 Derivatives of Amino Acids and Peptides.- 1.5 Proteins as Substrates of Proteases.- 1.6 Water.- 1.7 Conclusion.- 2 Enzymes.- 2.1 Classification.- 2.2 Distribution.- 2.3 Characteristics of Certain Types of Amide Hydrolases.- 2.4 Primary Structure.- 2.5 Spatial Structure.- 2.6 Active Sites.- 2.7 Conformational Mobility of Enzymes.- 2.8 Proteolytic Activity of Enzymes Other than Amide Hydrolases. Catalytically Active Antibodies.- 2.9 Conclusion.- 3 Nonenzymatic Hydrolysis. Models.- 3.1 Thermodynamics.- 3.2 Kinetics.- 3.3 Mechanism.- 3.4 Catalysis.- 3.5 Conclusion.- 4 Enzyme Hydrolysis. Phenomenology.- 4.1 Enzyme Kinetics.- 4.2 Relationship of Rate and Equilibrium.- 4.3 Specificity.- 4.3.3 Stereospecificity.- 4.4 Efficiency.- 4.5 Comparison of Amide Hydrolase Efficiency and Specificity.- 4.6 Effect of Amide Hydrolases Modification on the Activity.- 4.7 Synthetic Activity of Amide Hydrolases.- 4.8 Unusual and Side Reactions Catalyzed by Amide Hydrolases.- 4.9 Conclusion.- 5 Regulation and Effect of External Factors.- 5.1 Zymogens and Their Activation.- 5.2 The Influence of pH.- 5.3 The Influence of Ions and Ionic Strength of the Solution.- 5.4 The Effect of Organic Solvents.- 5.5 The Kinetic Isotope Effect of the Solvent.- 5.6 The Effect of Temperature and Pressure.- 5.7 Cryoenzymology of Amide Hydrolases.- 5.8 Micellar Enzymology.- 5.9 Inhibitors.- 5.10 Activation.- 5.11 Allosteric Effectors.- 5.12 Autolysis.- 5.13 Conclusion.- 6 Enzyme-Substrate Complexes.- 6.1 The Forces of Interaction.- 6.2 Kinetics of the Complex Formation.- 6.3 Thermodynamics.- 6.4 Conformational Changes.- 6.5 Structure of the Complexes.- 6.6 Evaluation of the Overall Energy of the Enzyme-Substrate Interaction.- 6.7 Conclusion.- 7 Chemical Transformation of the Substrate.- 7.1 The State of Catalytically Active Groups.- 7.2 The Charge Relay System.- 7.3 The State of the Cleavable Substrate Group.- 7.4 Covalent or General Base Catalysis?.- 7.5 Electrophile.- 7.6 Nucleophilic Attack. Elementary Step.- 7.7 Tetrahedral Intermediate.- 7.8 Proton Transfer and Decomposition of Tetrahedral Intermediate.- 7.9 Acylenzymes and Enzyme-Product Complexes.- 7.10 Comparison of Enzymatic Hydrolysis Mechanisms.- 7.11 Some Aspects of Evolution of Chemical Mechanisms of Amide Hydrolases.- 7.12 Conclusion.- 8 Specificity and Efficiency. Concepts and Hypotheses.- 8.1 General Considerations.- 8.2 Factors of Catalysis.- 8.3 Theories and Hypotheses. Destabilization of the Ground State.- 8.4 Stabilization of the Transition State.- 8.5 Enzyme — “Machine”.- 8.6 Quantum-Chemical Description of Enzymatic Reactions.- 8.7 “Ideal” Enzyme.- 8.8 Ground State of the Elementary Step of Enzymatic and Model Reactions.- 8.9 Enzyme Does Not Decrease Activation Energy of the Elementary Step of the Chemical Reaction.- 8.10 Approaches to the General Theory of Proteolysis.- 8.11 Conclusion.- References.