Introduction to Enzyme and Coenzyme Chemistry (3rd Ed.)
Auteur : Bugg T. D. H.
Enzymes are giant macromolecules which catalyse biochemical reactions. They are remarkable in many ways. Their three-dimensional structures are highly complex, yet they are formed by spontaneous folding of a linear polypeptide chain. Their catalytic properties are far more impressive than synthetic catalysts which operate under more extreme conditions. Each enzyme catalyses a single chemical reaction on a particular chemical substrate with very high enantioselectivity and enantiospecificity at rates which approach ?catalytic perfection?. Living cells are capable of carrying out a huge repertoire of enzyme-catalysed chemical reactions, some of which have little or no precedent in organic chemistry.
The popular textbook Introduction to Enzyme and Coenzyme Chemistry has been thoroughly updated to include information on the most recent advances in our understanding of enzyme action, with additional recent examples from the literature used to illustrate key points. A major new feature is the inclusion of two-colour figures, and the addition of over 40 new figures of the active sites of enzymes discussed in the text, in order to illustrate the interplay between enzyme structure and function.
This new edition provides a concise but comprehensive account from the perspective of organic chemistry, what enzymes are, how they work, and how they catalyse many of the major classes of enzymatic reactions, and will continue to prove invaluable to both undergraduate and postgraduate students of organic, bio-organic and medicinal chemistry, chemical biology, biochemistry and biotechnology.
Preface ix
Representation of Protein Three-Dimensional Structures x
1 From Jack Beans to Designer Genes 1
1.1 Introduction 1
1.2 The discovery of enzymes 1
1.3 The discovery of coenzymes 3
1.4 The commercial importance of enzymes in biosynthesis and biotechnology 3
1.5 The importance of enzymes as targets for drug discovery 6
2 All Enzymes Are Proteins 7
2.1 Introduction 7
2.2 The structures of the L-α-amino acids 7
2.3 The primary structure of polypeptides 9
2.4 Alignment of amino acid sequences 11
2.5 Secondary structures found in proteins 12
2.6 The folded tertiary structure of proteins 15
2.7 Enzyme structure and function 17
2.8 Metallo-enzymes 20
2.9 Membrane-associated enzymes 21
2.10 Glycoproteins 23
3 Enzymes Are Wonderful Catalysts 26
3.1 Introduction 26
3.2 A thermodynamic model of catalysis 28
3.3 Proximity effects 30
3.4 The importance of transition state stabilisation 32
3.5 Acid/base catalysis in enzymatic reactions 36
3.6 Nucleophilic catalysis in enzymatic reactions 40
3.7 The use of strain energy in enzyme catalysis 44
3.8 Desolvation of substrate and active site nucleophiles 45
3.9 Catalytic perfection 46
3.10 The involvement of protein dynamics in enzyme catalysis 47
4 Methods for Studying Enzymatic Reactions 50
4.1 Introduction 50
4.2 Enzyme purification 50
4.3 Enzyme kinetics 52
4.4 The stereochemical course of an enzymatic reaction 59
4.5 The existence of intermediates in enzymatic reactions 64
4.6 Analysis of transition states in enzymatic reactions 68
4.7 Determination of active site catalytic groups 71
5 Hydrolytic and Group Transfer Enzymes 77
5.1 Introduction 77
5.2 The peptidases 79
CASE STUDY: HIV-1 protease 90
5.3 Esterases and lipases 92
5.4 Acyl transfer reactions in biosynthesis (coenzyme A) 93
5.5 Enzymatic phosphoryl transfer reactions 95
5.6 Adenosine 5’-triphosphate (ATP) 101
5.7 Enzymatic glycosyl transfer reactions 102
5.8 Methyl group transfer: use of S-adenosyl methionine and tetrahydrofolate
coenzymes for one-carbon transfers 107
6 Enzymatic Redox Chemistry 115
6.1 Introduction 115
6.2 Nicotinamide adenine dinucleotide-dependent dehydrogenases 117
6.3 Flavin-dependent dehydrogenases and oxidases 122
6.4 Flavin-dependent mono-oxygenases 128
6.5 CASE STUDY: Glutathione and trypanothione reductases 129
6.6 Deazaflavins and pterins 133
6.7 Iron-sulphur clusters 135
6.8 Metal-dependent mono-oxygenases 136
6.9 α-Ketoglutarate-dependent dioxygenases 140
6.10 Non-heme iron-dependent dioxygenases 141
7 Enzymatic Carbon–Carbon Bond Formation 148
7.1 Introduction 148
Carbon–carbon bond formation via carbanion equivalents 149
7.2 Aldolases 149
CASE STUDY: Fructose 1,6-bisphosphate aldolase 150
7.3 Claisen enzymes 153
7.4 Assembly of fatty acids and polyketides 156
7.5 Carboxylases: Use of biotin 158
7.6 Ribulose bisphosphate carboxylase/oxygenase (Rubisco) 161
7.7 Vitamin K-dependent carboxylase 163
7.8 Thiamine pyrophosphate-dependent enzymes 165
Carbon–carbon bond formation via carbocation intermediates 168
7.9 Terpene cyclases 168
Carbon–carbon formation through radical intermediates 173
7.10 Phenolic radical couplings 173
8 Enzymatic Addition/Elimination Reactions 181
8.1 Introduction 181
8.2 Hydratases and dehydratases 182
8.3 Ammonia lyases 187
8.4 Elimination of phosphate and pyrophosphate 190
8.5 CASE STUDY: 5-Enolpyruvyl shikimate 3-phosphate (EPSP) synthase 191
9 Enzymatic Transformations of Amino Acids 197
9.1 Introduction 197
9.2 Pyridoxal 5’-phosphate-dependent reactions at the α-position 197
9.3 CASE STUDY: Aspartate aminotransferase 201
9.4 Reactions at the β- and γ-positions of amino acids 204
9.5 Serine hydroxymethyltransferase 206
9.6 N-Pyruvoyl-dependent amino acid decarboxylases 208
9.7 Imines and enamines in alkaloid biosynthesis 208
10 Isomerases 213
10.1 Introduction 213
10.2 Cofactor-independent racemases and epimerases 213
10.3 Keto-enol tautomerases 216
10.4 Allylic isomerases 217
10.5 CASE STUDY: Chorismate mutase 219
11 Radicals in Enzyme Catalysis 225
11.1 Introduction 225
11.2 Vitamin B12-dependent rearrangements 225
11.3 The involvement of protein radicals in enzyme catalysis 229
11.4 S-adenosyl-methionine-dependent radical reactions 232
11.5 Biotin synthase and sulphur insertion reactions 233
11.6 Radical chemistry in DNA repair enzymes 234
11.7 Oxidised amino acid cofactors and quinoproteins 238
12 Non-Enzymatic Biological Catalysis 242
12.1 Introduction 242
12.2 Catalytic RNA 242
12.3 Catalytic antibodies 246
12.4 Synthetic enzyme models 251
Appendix 1: Cahn-Ingold-Prelog Rule for Stereochemical Nomenclature 258
Appendix 2: Amino Acid Abbreviations 260
Appendix 3: A Simple Demonstration of Enzyme Catalysis 261
Appendix 4: Answers to Problems 263
Index 271
Professor Bugg is Professor of Biological Chemistry at the University of Warwick. Following his PhD studies with Dr C. Abell at the University of Cambridge he spent two years as a SERC/NATO postdoctoral research fellow in the laboratory of Professor CT Walsh at Harvard Medical School. In 1991 he began his academic career as a lecturer in organic chemistry at the University of Southampton, before moving to Warwick in 1999. His research interests are in the study of enzyme mechanisms, principally enzymes involved in the bacterial degradation of aromatic compounds, and enzymes involved in bacterial peptidoglycan biosynthesis. He has published approximately 100 journal publications since 1988, is the author of "An Introduction to Enzyme and Coenzyme Chemistry" (2 editions), and a contributor to "Comprehensive Natural Products Chemistry", and "Encyclopaedia of Chemical Biology" (for which he is on the Advisory Board).
Date de parution : 08-2012
Ouvrage de 280 p.
17.3x25.2 cm
Date de parution : 08-2012
Ouvrage de 304 p.
17x24.5 cm
Mots-clés :
enzymes; reactions; macromolecules; catalyse biochemical; ways; many; complex; structures; threedimensional; highly; linear; spontaneous; polypeptide chain; catalytic; synthetic; extreme; properties; catalysts; conditions; impressive; single
