Introduction to Enzyme and Coenzyme Chemistry, 2nd Edition

by Tim Bugg (Professor of Biological Chemistry, Department of Chemistry, University of Warwick, UK)

• ISBN13: 9781405114523
• ISBN10: 1405114525
• eBook ISBN(s): 9781405148009
• Edition: 2nd
• Format: Paperback
• Copyright: 2004-10-01
• Publisher: Wiley-Blackwell

Summary

Enzyme catalysis is a topic of fundamental importance in organic, bio-organic and medicinal chemistry. This new edition of a very popular textbook provides a concise introduction to the underlying principles and mechanisms of enzyme and coenzyme action from a chemical perspective. Whilst retaining the overall structure of the first edition preliminary chapters describe the basic principles of enzyme structure and catalysis moving through to detailed discussions of the major classes of enzyme processes in the later chapters the book has been thoroughly updated to include information on the most recent advances in our understanding of enzyme action. A major feature of the second edition is the inclusion of two-colour figures of the active sites of enzymes discussed in the text, in order to illustrate the interplay between enzyme structure and function. Problems, with outline answers, at the end of each chapter give the student the chance to the check their understanding of the material. As a concise but comprehensive account, Introduction to Enzyme and Coenzyme Chemistry will continue to prove invaluable to both undergraduate and postgraduate students of organic, bio-organic and medicinal chemistry. Tim Bugg is professor of biological chemistry in the Department of Chemistry, University of Warwick, UK. Also Available from Blackwell Publishing Experimental Organic Chemistry: Standard and Microscale Second Edition L M Harwood, C J Moody and J M Percy Softback (0 632 04819 0), 728 pages Heterocyclic Chemistry Fourth Edition J A Joule and K Mills Softback (0 632 05453 0), 608 pages Introduction to Free Radical Chemistry A F Parsons Softback (0 632 05292 9), 248 pages

Author Biography

Tim Bugg is Professor of Biological Chemistry in the Department of Chemistry, University of Warwick, UK.

Table of Contents

Preface	ix
Representation of Protein Three-Dimensional Structures	x
From Jack Beans to Designer Genes	1	(7)
Introduction	1	(1)
The discovery of enzymes	1	(2)
The discovery of coenzymes	3	(1)
The commercial importance of enzymes in biosynthesis and biotechnology	3	(3)
The importance of enzymes as targets for drug discovery	6	(2)
All Enzymes are Proteins	8	(21)
Introduction	8	(1)
The structures of the L-α-amino acids	8	(2)
The primary structure of polypeptides	10	(2)
Alignment of amino acid sequences	12	(1)
Secondary structures found in proteins	13	(3)
The folded tertiary structure of proteins	16	(3)
Enzyme structure and function	19	(3)
Metallo-enzymes	22	(1)
Membrane-associated enzymes	23	(1)
Glycoproteins	24	(5)
Enzymes are Wonderful Catalysts	29	(22)
Introduction	29	(2)
A thermodynamic model of catalysis	31	(2)
Proximity effects	33	(3)
The importance of transition state stabilisation	36	(1)
Acid/base catalysis in enzymatic reactions	37	(4)
Nucleophilic catalysis in enzymatic reactions	41	(4)
The use of strain energy in enzyme catalysis	45	(2)
Catalytic perfection	47	(1)
The involvement of protein dynamics in enzyme catalysis	47	(4)
Methods for Studying Enzymatic Reactions	51	(30)
Introduction	51	(1)
Enzyme purification	51	(3)
Enzyme kinetics	54	(6)
The stereochemical course of an enzymatic reaction	60	(8)
The existence of intermediates in enzymatic reactions	68	(3)
Analysis of transition states in enzymatic reactions	71	(4)
Determination of active site catalytic groups	75	(6)
Enzymatic Hydrolysis and Group Transfer Reactions	81	(40)
Introduction	81	(1)
The peptidases	82	(16)
Case Study: HIV-1 protease	96	(2)
Esterases and lipases	98	(1)
Acyl transfer reactions in biosynthesis: use of coenzyme A (CoA)	99	(3)
Enzymatic phosphoryl transfer reactions	102	(4)
Adenosine 5'-triphosphate	106	(3)
Enzymatic glycosyl transfer reactions	109	(3)
Methyl group transfer: use of S-adenosyl methionine and tetrahydrofolate coenzymes for one-carbon transfers	112	(9)
Enzymatic Redox Chemistry	121	(35)
Introduction	121	(2)
Nicotinamide adenine dinucleotide-dependent dehydrogenases	123	(6)
Flavin-dependent dehydrogenases and oxidases	129	(5)
Flavin-dependent mono-oxygenases	134	(3)
Case Study: Glutathione and trypanothione reductases	137	(4)
Deazaflavins and pterins	141	(1)
Iron-sulphur clusters	142	(1)
Metal-dependent mono-oxygenases	143	(4)
α-Ketoglutarate-dependent dioxygenases	147	(1)
Non-haem iron-dependent dioxygenases	148	(8)
Enzymatic Carbon-Carbon Bond Formation	156	(37)
Introduction	156	(2)
Carbon-carbon bond formation via carbanion equivalents	158	(1)
Aldolases	158	(6)
Case Study: Fructose-1,6-bisphosphate aldolase	158	(6)
Claisen enzymes	164	(2)
Assembly of fatty acids and polyketides	166	(4)
Carboxylases: use of biotin	170	(1)
Ribulose bisphosphate carboxylase/oxygenase (Rubisco)	171	(2)
Vitamin K-dependent carboxylase	173	(3)
Thiamine pyrophosphate-dependent enzymes	176	(3)
Carbon-carbon bond formation via carbocation intermediates	179	(1)
Terpene cyclases	179	(5)
Carbon-carbon bond formation via radical intermediates	183	(1)
Phenolic radical couplings	184	(9)
Enzymatic Addition/Elimination Reactions	193	(17)
Introduction	193	(1)
Hydratases and dehydratases	194	(5)
Ammonia lyases	199	(3)
Elimination of phosphate and pyrophosphate	202	(2)
Case Study: 5-Enolpyruvyl-shikimate-3-phosphate (EPSP) synthase	204	(6)
Enzymatic Transformations of Amino Acids	210	(17)
Introduction	210	(1)
Pyridoxal 5'-phosphate-dependent reactions at the α-position of amino acids	211	(4)
Case Study: Aspartate aminotransferase	215	(3)
Reactions at β- and γ-positions of amino acids	218	(2)
Serine hydroxymethyltransferase	220	(2)
N-Pyruvoyl-dependent amino acid decarboxylases	222	(1)
Imines and enamines in alkaloid biosynthesis	222	(5)
Isomerases	227	(13)
Introduction	227	(1)
Cofactor-independent racemases and epimerases	227	(3)
Keto--enol tautomerases	230	(1)
Allylic isomerases	231	(2)
Case Study: Chorismate mutase	233	(7)
Radicals in Enzyme Catalysis	240	(15)
Introduction	240	(1)
Vitamin B12-dependent rearrangements	240	(4)
The involvement of protein radicals in enzyme catalysis	244	(2)
S-adenosyl methionine-dependent radical reactions	246	(3)
Biotin synthase and sulphur insertion reactions	249	(1)
Oxidised amino acid cofactors and quinoproteins	250	(5)
Non-Enzymatic Biological Catalysis	255	(17)
Introduction	255	(1)
Catalytic RNA	255	(4)
Catalytic antibodies	259	(6)
Synthetic enzyme models	265	(7)
Appendices	272	(13)
1. Cahn-Ingold-Prelog rule for stereochemical nomenclature	272	(2)
2. Amino acid abbreviations	274	(1)
3. A simple demonstration of enzyme catalysis	275	(2)
4. Answers to problems	277	(8)
Index	285