Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

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All Enzymes are Proteins 11 arranged in a speciWc linear sequence. To give some idea of size, a typical gene might consist of a sequence of 1000 nucleotide bases encoding the information for the synthesis of a protein of approximately 330 amino acids, whose molecular weight would be 35–40 kDa. How is the sequence encoded First the deoxyribonucleotide sequence of the DNA strand is transcribed into messenger ribonucleic acid (mRNA) containing the corresponding ribonucleotides adenine (A), cytidine (C), guanine (G) and uridine (U, corresponding to dT). The RNA strand is then translated into protein by the biosynthetic machinery known as ribosomes, as shown in Figure 2.4. The RNA sequence is translated into protein in sets of three nucleotide bases, one set of three bases being known as a ‘triplet codon’. Each codon encodes a single amino acid. The code deWning which amino acid is derived from which triplet codon is the ‘universal genetic code’, shown in Figure 2.5. This universal code is followed by the protein biosynthetic machinery of all organisms. As an example we shall consider in Figure 2.6 the N-terminal peptide sequence Met–Ala–Phe–Ser–Asp illustrated in Figure 2.3. The Wrst amino acid at the N-terminus of each protein is always methionine, whose triplet codon is AUG. The next triplet GCC encodes alanine; UUC encodes phenylalanine; UCC encodes serine; and GAC encodes aspartate. Translation then continues in triplets until one of three ‘stop’ codons is reached; at this point protein translation stops. Note that for most amino acids there is more than one possible codon: thus if UUC is changed to UUU, phenylalanine is still encoded, but if changed to UCC then serine is encoded as above. In this way the nucleotide sequence of the gene is translated into the amino acid sequence of the encoded protein. An important practical consequence is that the amino acid sequence of an enzyme can be determined by nucleotide sequencing of the corresponding gene, which is now the most convenient way to determine a protein sequence. gene DNA 5 3 promoter site RNA polymerase ribonucleoside triphosphates mRNA 5 3 ribosome binding site ribosomes amino acyl-transfer RNAs Protein + − H 3 N-aa 1 -aa 2 -aa 3 -aa 4 -............-aa n-1 -aa n -CO 2 Figure 2.4 Pathway for protein biosynthesis.
12 Chapter 2 AAA Lys ACA Thr AGA Arg AUA Ile AAG Lys ACG Thr AGG Arg AUG Met AAC Asn ACC Thr AGC Ser AUC Ile AAU Asn ACU Thr AGU Ser AUU Ile CAA Gln CCA Pro CGA Arg CUA Leu CAG Gln CCG Pro CGG Arg CUG Leu CAC His CCC Pro CGC Arg CUC Leu CAU His CCU Pro CGU Arg CUU Leu GAA Glu GCA Ala GGA Gly GUA Val GAG Glu GCG Ala GGG Gly GUG Val GAC Asp GCC Ala GGC Gly GUC Val GAU Asp GCU Ala GGU Gly GUU Val UAA Stop UCA Ser UGA Stop UUA Leu UAG Stop UCG Ser UGG Trp UUG Leu UAC Tyr UCC Ser UGC Cys UUC Phe UAU Tyr UCU Ser UGU Cys UUU Phe Figure 2.5 The universal genetic code. start codon mRNA....GGATCAUGGCCUUCUCCGACUACCGGA.... AUG GCC UUC UCC GAC ... Met Ala Phe Ser Asp Figure 2.6 Translation of mRNA into protein. 2.4 Alignment of amino acid sequences Most biochemical reactions are found in more than one organism, in some cases in all living cells. If the enzymes which catalyse the same reaction in diVerent organisms are puriWed and their amino acid sequences are determined, then we often see similarity between the two sequences. The degree of similarity is usually highest in enzymes from organisms which have evolved recently on an evolutionary timescale. The implication of such an observation is that the two enzymes have evolved divergently from a common ancestor. Over a long period of time, changes in the DNA sequence of a gene can occur by random mutation or by several types of rare mistakes in DNA replication. Many of these mutations will lead to a change in the encoded protein sequence in such a way that the mutant protein is inactive. These mutations are likely to be lethal to the cell and are hence not passed down to the next generation. However, mutations which result in minor modiWcations to non-essential residues in an enzyme will have little eVect on the activity of the enzyme, and will therefore be passed onto the next generation. So if we look at an alignment of amino acid sequences of ‘related’ enzymes from diVerent organisms, we would expect that catalytically important amino
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 and 18: 6 Chapter 1 has very diVerent biolo
Page 19 and 20: 2 All Enzymes are Proteins 2.1 Intr
Page 21: 10 Chapter 2 (Gln). There are three
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
Page 71 and 72: 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
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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 +
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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
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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
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284 Appendix 4 (b) Formation of rad
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286 Index b-hydroxydecanoyl thioest
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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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