Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

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From Jack Beans to Designer Genes 7 enzyme targets, and has led to the development of powerful molecular modelling software for analysis of enzyme structure and de novo design of enzyme inhibitors. The next two chapters are ‘theory’ chapters on enzyme structure and enzyme catalysis, followed by a ‘practical’ chapter on methods used to study enzymatic reactions. Chapters 5–11 cover each of the major classes of enzymatic reactions, noting each of the coenzymes used for enzymatic reactions. Finally, there is a brief introduction in Chapter 12 to other types of biological catalysis. In cases where discussion is brief the interested reader will Wnd references to further reading at the end of each chapter. Further reading Historical development of enzymology T.D.H. Bugg (2001) The development of mechanistic enzymology in the 20th century. Nat. Prod. Reports, 18, 465–93. Enzymes in biosynthesis and biotechnology J. Mann (1987) Secondary Metabolism, 2nd edition. Clarendon Press, Oxford. C.H. Wong & G.M. Whitesides (1994) Enzymes in Synthetic Organic Chemistry. Pergamon, Oxford. Medicinal chemistry G.L. Patrick (2001) An Introduction to Medicinal Chemistry, 2nd edition. OUP, Oxford. R.B. Silverman (2001) The Organic Chemistry of Drug Design and Drug Action. Academic Press, San Diego.
2 All Enzymes are Proteins 2.1 Introduction Enzymes are giant molecules. Their molecular weight varies from 5000 to 5 000 000 Da, with typical values in the range 20 000–100 000 Da. At Wrst sight this size suggests a bewildering complexity of structure, yet we shall see that enzymes are structurally assembled in a small number of steps in a fairly simple way. Enzymes belong to a larger biochemical family of macromolecules known as proteins. The common feature of proteins is that they are polypeptides: their structure is made up of a linear sequence of a-amino acid building blocks joined together by amide linkages. This linear polypeptide chain then ‘folds’ to give a unique three-dimensional structure. 2.2 The structures of the L-a-amino acids Proteins are composed of a family of 20 a-amino acid structural units whose general structure is shown in Figure 2.1. a-Amino acids are chiral molecules: that is, their mirror image is not superimposable upon the original molecule. Each a-amino acid can be found as either the l- ord-isomer depending on the conWguration at the a-carbon atom (except for glycine where R5H). All proteins are composed only of l-amino acids, consequently enzymes are inherently chiral molecules – an important point. d-amino acids are rare in biological systems, although they are found in a number of natural products and notably in the peptidoglycan layer of bacterial cell walls (see Chapter 9). The a-amino acids used to make up proteins number only 20, whose structures are shown in Figure 2.2. The diVerences between these 20 lie in the nature of the side chain R. The simplest amino acids are glycine (abbreviated Gly or simply G), which has no side chain, and alanine (Ala or A), whose side chain is a methyl group. A number of side chains are hydrophobic (‘water-hating’) in character, for example the thioether of methionine (Met); the branched aliphatic side chains of valine (Val), leucine (Leu) and isoleucine (Ile); and the aromatic H R R H H 2 N CO 2 H H 2 N CO 2 H general structure of an L-α-amino acid general structure of a D-α-amino acid Figure 2.1 General structure of l- and d-amino acids. 8
Page 1 and 2: Introduction to Enzyme and Coenzyme
Page 4 and 5: Introduction to Enzyme and Coenzyme
Page 6 and 7: Contents Preface Representation of
Page 8: Contents vii 8 Enzymatic Addition/E
Page 11 and 12: Representation of Protein Three-Dim
Page 13 and 14: 2 Chapter 1 H 2 N O NH 2 + H 2 O Ja
Page 15 and 16: 4 Chapter 1 Table 1.1 The vitamins.
Page 17: 6 Chapter 1 has very diVerent biolo
Page 21 and 22: 10 Chapter 2 (Gln). There are three
Page 23 and 24: 12 Chapter 2 AAA Lys ACA Thr AGA Ar
Page 25 and 26: 14 Chapter 2 H N O H N O Figure 2.8
Page 27 and 28: 16 Chapter 2 (a) (b) Figure 2.12 St
Page 29 and 30: 18 Chapter 2 Figure 2.14 Structure
Page 31 and 32: 20 Chapter 2 (a) X Y Enzyme + Subst
Page 33 and 34: 22 Chapter 2 maintaining protein te
Page 35 and 36: 24 Chapter 2 surface glycoprotein g
Page 37 and 38: 26 Chapter 2 O-linked glycosylation
Page 39 and 40: 28 Chapter 2 Metalloproteins I. Ber
Page 41 and 42: 30 Chapter 3 O N H R CO 2 H acylase
Page 43 and 44: 32 Chapter 3 (a) Free energy uncata
Page 45 and 46: 34 Chapter 3 Ester k rel Effective
Page 47 and 48: 36 Chapter 3 3.4 The importance of
Page 49 and 50: 38 Chapter 3 pKa Tyrosine CH 2 O H
Page 51 and 52: 40 Chapter 3 glycoside hydrolysis (
Page 53 and 54: 42 Chapter 3 O O Glu 143 O − R H
Page 55 and 56: 44 Chapter 3 the hydroxyl groups of
Page 57 and 58: 46 Chapter 3 E + S E + S ES' ES ‘
Page 59 and 60: 48 Chapter 3 Examination of protein
Page 61 and 62: 50 Chapter 3 (Note: Similar results
Page 63 and 64: 52 Chapter 4 (1) Direct UV (2) Radi
Page 65 and 66: 54 Chapter 4 Figure 4.3 PuriWcation
Page 67 and 68: 56 Chapter 4 The two kinetic consta
Page 69 and 70:
58 Chapter 4 Lineweaver−Burk Plot
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60 Chapter 4 E + S K i EI+ I ES E +
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62 Chapter 4 (2) by treatment with
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64 Chapter 4 In general the stereoc
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H D T CO 2 H CO − 2 T HO D H −
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68 Chapter 4 4.5 The existence of i
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70 Chapter 4 18O 18O 18 O O P O −
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72 Chapter 4 If a reaction involves
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74 Chapter 4 O D H ketosteroid isom
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76 Chapter 4 Table 4.3 Group speciW
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78 Chapter 4 [S] (mM) Rate of produ
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80 Chapter 4 Enzyme kinetics I.H. S
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82 Chapter 5 O = C NHR peptidase H
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84 Chapter 5 non-speciWc protease c
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86 Chapter 5 His 57 His 57 Asp 102
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88 Chapter 5 Other serine proteases
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90 Chapter 5 Figure 5.8 Structure o
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92 Chapter 5 now predominate Perhap
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OH R O Zn 2+ O O O Ph Glu 270 H 2 N
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96 Chapter 5 CASE STUDY: HIV-1 prot
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98 Chapter 5 HO Transition state pe
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100 Chapter 5 The aminoacyl group o
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102 Chapter 5 5.5 Enzymatic phospho
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104 Chapter 5 Figure 5.29 Structure
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Page 119 and 120:
108 Chapter 5 Adenosine 5 0 -tripho
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110 Chapter 5 functional group. Gly
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112 Chapter 5 CH 2 OH O RO HO OH O
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114 Chapter 5 to these atoms that t
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116 Chapter 5 Problems (1) Using pa
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118 Chapter 5 (6) Retaining glycosi
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120 Chapter 5 J.R. Knowles (1980) E
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122 Chapter 6 +1.0 Redox potential
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Table 6.1 Classes of redox enzymes.
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126 Chapter 6 An important point is
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128 Chapter 6 O H − OH − O OH H
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130 Chapter 6 one-electron transfer
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132 Chapter 6 (a) R N H + N O R N H
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134 Chapter 6 Inactivation by trany
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Page 149 and 150:
138 Chapter 6 (a) (b) Figure 6.23 S
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140 Chapter 6 glutathione called tr
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142 Chapter 6 neither has a stable
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144 Chapter 6 of the haem cofactor
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146 Chapter 6 Figure 6.33 Active si
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148 Chapter 6 HO H N N O O H N prol
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150 Chapter 6 R R R O 2 , Fe 2+ O O
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152 Chapter 6 CoA. Explain these re
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154 Chapter 6 NADH models O. Almars
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7 Enzymatic Carbon-Carbon Bond Form
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158 Chapter 7 O H − OH O − O H
Page 171 and 172:
Page 173 and 174:
162 Chapter 7 Figure 7.6 Active sit
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164 Chapter 7 7.3 Claisen enzymes I
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166 Chapter 7 CoAS O EnzB − H D T
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168 Chapter 7 onto the acetyl-thioe
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170 Chapter 7 In the case of erythr
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172 Chapter 7 O HO O − O ATP ADP
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174 Chapter 7 CO 2 − vitamin K-de
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176 Chapter 7 7.8 Thiamine pyrophos
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178 Chapter 7 HN N + N H NH S O OPP
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180 Chapter 7 O OH OH camphor geran
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182 Chapter 7 CH 3 * OPP (−)pinen
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Page 197 and 198:
186 Chapter 7 C C C C C O OCH 3 C H
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188 Chapter 7 AcO HO HO NHAc O OH +
Page 201 and 202:
190 Chapter 7 (9) Usnic acid is a n
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192 Chapter 7 Radical couplings W.M
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194 Chapter 8 C-O cleavage H E1 H C
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196 Chapter 8 leads to the formatio
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198 Chapter 8 aconitase citrate cis
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200 Chapter 8 *H R H H CO 2 − NH
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202 Chapter 8 EnzB − 2 H − O 2
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204 Chapter 8 involves no change in
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206 Chapter 8 Glyphosate H H N CO
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208 Chapter 8 (5) Chorismic acid (s
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9 Enzymatic Transformations of Amin
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CO − − 2 CO 2 H H CO 2 − N +
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214 Chapter 9 - BEnz CO − 2 Cl H
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216 Chapter 9 Arg 292 Arg 292 Lys 2
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218 Chapter 9 Arg 292 Asp 292 HN H
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220 Chapter 9 S − B 1 Enz H − C
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222 Chapter 9 9.6 N-Pyruvoyl-depend
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224 Chapter 9 The biosyntheses of n
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226 Chapter 9 Further reading Gener
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228 Chapter 10 B 1 - H + NH 3 CO
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230 Chapter 10 ‘low-barrier’ +
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232 Chapter 10 H S C 6 H 13 HN His
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234 Chapter 10 O H NH 3 CO 2 − CO
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236 Chapter 10 sub-units. Each sub-
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238 Chapter 10 Further reading Gene
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11 Radicals in Enzyme Catalysis 11.
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242 Chapter 11 CH 2 Co III Ad H OH
Page 255 and 256:
244 Chapter 11 − O 2 C − O CO
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246 Chapter 11 H N H O 734 H N H PF
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248 Chapter 11 H H* + H + H 3 N CO
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250 Chapter 11 O HN NH + H 3 N H 3
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252 Chapter 11 cofactor is involved
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254 Chapter 11 Protein Radicals J.
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256 Chapter 12 self-splicing reacti
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258 Chapter 12 Figure 12.2 Structur
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260 Chapter 12 antigen combining si
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262 Chapter 12 R O OR' OH − R O
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264 Chapter 12 CO 2 − − O 2 C O
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266 Chapter 12 (1) Selective substr
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268 Chapter 12 HO O HO OH HO OH O O
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270 Chapter 12 Problems (1) How rev
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Appendix 1: Cahn-Ingold-Prelog Rule
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Appendix 2: Amino Acid Abbreviation
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276 Appendix 3 Preparation of orang
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278 Appendix 4 (2) Intramolecular a
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280 Appendix 4 from water at a-posi
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282 Appendix 4 Chapter 8 (1) Treat
Page 295 and 296:
284 Appendix 4 (b) Formation of rad
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286 Index b-hydroxydecanoyl thioest
Page 299 and 300:
288 Index glycosylation 26-7 glysop
Page 301 and 302:
290 Index phenylalanine ammonia lya
Page 303:
292 Index transition states 31-2 an
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