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Enzymatic Carbon–Carbon Bond Formation 183 Pentalenene synthase F L D D F L D Trichodiene synthase V L D D S K D Aristolochene synthase L I D D V L E Casbene synthase L I D D T I D Limonene synthase V I D D I Y D Farnesyl PP synthase V Q D D I L D Geranylgeranyl PP synthase I A D D Y H N Consensus D D X X(D) O H N H O O O − N H O − O H O Mg 2+ − O O − R O P O P O − O O Figure 7.35 Mg 2þ -pyrophosphate binding motif. How do these cyclase enzymes control the precise regiochemistry and stereochemistry of these multi-step cyclisations In 1997 the crystal structure of pentalenene synthase was solved. The active site consists of a conical hydrophobic cleft, Xanked by six a-helices, lined with aromatic and non-polar residues. The DDXXD motif is located near the upper edge of the cavity, as shown in Figure 7.36. The identity of the catalytic base has not yet been identiWed, but replacement of Phe-76 or Phe-77 by alanine gave at least a 10-fold reduction in activity, suggesting that they may stabilise carbocationic intermediates through -cation interactions. The presence of aromatic residues in key positions of the wall of terpene cyclase active sites suggests that the -cation interaction, shown in Figure 7.37, may have an important role in the speciWc stabilisation of the carbocation intermediates. Carbon–carbon bond formation via radical intermediates In Chapter 6 we have seen how redox enzymes are able to generate radical intermediates in enzyme-catalysed reactions. In certain instances these radical intermediates are used for carbon–carbon bond formation reactions. The two examples which we shall examine are phenol radical couplings used in natural product biosynthesis and in lignin biosynthesis.
184 Chapter 7 Figure 7.36 Structure of pentalanene synthase (PDB Wle 1PS1), showing the active site residues Asp- 80, Asp-81, Asp-84 (DDXXD motif, top), Phe-76 and Phe-77 in red. C+ Phe Figure 7.37 p-Cation interaction. 7.10 Phenolic radical couplings Certain aromatic natural products are formed by the radical coupling of two phenol precursors in an enzyme-catalysed process. In some cases the enzymes are blue copper proteins (the characteristic colour due to the metal cofactor). For example, the phenol radical coupling of sulochrin shown in Figure 7.38 is catalysed by a 157-kDa oxidase enzyme containing six atoms of copper. The
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Introduction to Enzyme and Coenzyme
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Introduction to Enzyme and Coenzyme
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Contents Preface Representation of
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Contents vii 8 Enzymatic Addition/E
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Representation of Protein Three-Dim
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2 Chapter 1 H 2 N O NH 2 + H 2 O Ja
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4 Chapter 1 Table 1.1 The vitamins.
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6 Chapter 1 has very diVerent biolo
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2 All Enzymes are Proteins 2.1 Intr
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10 Chapter 2 (Gln). There are three
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12 Chapter 2 AAA Lys ACA Thr AGA Ar
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14 Chapter 2 H N O H N O Figure 2.8
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16 Chapter 2 (a) (b) Figure 2.12 St
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18 Chapter 2 Figure 2.14 Structure
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20 Chapter 2 (a) X Y Enzyme + Subst
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22 Chapter 2 maintaining protein te
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24 Chapter 2 surface glycoprotein g
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26 Chapter 2 O-linked glycosylation
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28 Chapter 2 Metalloproteins I. Ber
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30 Chapter 3 O N H R CO 2 H acylase
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32 Chapter 3 (a) Free energy uncata
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34 Chapter 3 Ester k rel Effective
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36 Chapter 3 3.4 The importance of
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38 Chapter 3 pKa Tyrosine CH 2 O H
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40 Chapter 3 glycoside hydrolysis (
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42 Chapter 3 O O Glu 143 O − R H
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44 Chapter 3 the hydroxyl groups of
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46 Chapter 3 E + S E + S ES' ES ‘
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48 Chapter 3 Examination of protein
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50 Chapter 3 (Note: Similar results
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52 Chapter 4 (1) Direct UV (2) Radi
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54 Chapter 4 Figure 4.3 PuriWcation
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56 Chapter 4 The two kinetic consta
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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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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
Page 143 and 144: 132 Chapter 6 (a) R N H + N O R N H
Page 145 and 146: 134 Chapter 6 Inactivation by trany
Page 147 and 148: 136 Chapter 6 Figure 6.20 Structure
Page 149 and 150: 138 Chapter 6 (a) (b) Figure 6.23 S
Page 151 and 152: 140 Chapter 6 glutathione called tr
Page 153 and 154: 142 Chapter 6 neither has a stable
Page 155 and 156: 144 Chapter 6 of the haem cofactor
Page 157 and 158: 146 Chapter 6 Figure 6.33 Active si
Page 159 and 160: 148 Chapter 6 HO H N N O O H N prol
Page 161 and 162: 150 Chapter 6 R R R O 2 , Fe 2+ O O
Page 163 and 164: 152 Chapter 6 CoA. Explain these re
Page 165 and 166: 154 Chapter 6 NADH models O. Almars
Page 167 and 168: 7 Enzymatic Carbon-Carbon Bond Form
Page 169 and 170: 158 Chapter 7 O H − OH O − O H
Page 171 and 172: 160 Chapter 7 Figure 7.4 Structure
Page 173 and 174: 162 Chapter 7 Figure 7.6 Active sit
Page 175 and 176: 164 Chapter 7 7.3 Claisen enzymes I
Page 177 and 178: 166 Chapter 7 CoAS O EnzB − H D T
Page 179 and 180: 168 Chapter 7 onto the acetyl-thioe
Page 181 and 182: 170 Chapter 7 In the case of erythr
Page 183 and 184: 172 Chapter 7 O HO O − O ATP ADP
Page 185 and 186: 174 Chapter 7 CO 2 − vitamin K-de
Page 187 and 188: 176 Chapter 7 7.8 Thiamine pyrophos
Page 189 and 190: 178 Chapter 7 HN N + N H NH S O OPP
Page 191 and 192: 180 Chapter 7 O OH OH camphor geran
Page 193: 182 Chapter 7 CH 3 * OPP (−)pinen
Page 197 and 198: 186 Chapter 7 C C C C C O OCH 3 C H
Page 199 and 200: 188 Chapter 7 AcO HO HO NHAc O OH +
Page 201 and 202: 190 Chapter 7 (9) Usnic acid is a n
Page 203 and 204: 192 Chapter 7 Radical couplings W.M
Page 205 and 206: 194 Chapter 8 C-O cleavage H E1 H C
Page 207 and 208: 196 Chapter 8 leads to the formatio
Page 209 and 210: 198 Chapter 8 aconitase citrate cis
Page 211 and 212: 200 Chapter 8 *H R H H CO 2 − NH
Page 213 and 214: 202 Chapter 8 EnzB − 2 H − O 2
Page 215 and 216: 204 Chapter 8 involves no change in
Page 217 and 218: 206 Chapter 8 Glyphosate H H N CO
Page 219 and 220: 208 Chapter 8 (5) Chorismic acid (s
Page 221 and 222: 9 Enzymatic Transformations of Amin
Page 223 and 224: CO − − 2 CO 2 H H CO 2 − N +
Page 225 and 226: 214 Chapter 9 - BEnz CO − 2 Cl H
Page 227 and 228: 216 Chapter 9 Arg 292 Arg 292 Lys 2
Page 229 and 230: 218 Chapter 9 Arg 292 Asp 292 HN H
Page 231 and 232: 220 Chapter 9 S − B 1 Enz H − C
Page 233 and 234: 222 Chapter 9 9.6 N-Pyruvoyl-depend
Page 235 and 236: 224 Chapter 9 The biosyntheses of n
Page 237 and 238: 226 Chapter 9 Further reading Gener
Page 239 and 240: 228 Chapter 10 B 1 - H + NH 3 CO
Page 241 and 242: 230 Chapter 10 ‘low-barrier’ +
Page 243 and 244: 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
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290 Index phenylalanine ammonia lya
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292 Index transition states 31-2 an
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