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Radicals in Enzyme Catalysis 241 N NH 2 N H 2 N H 2 N O CH 2 O HO OH N H H 3 C H 3 C CONH 2 N O O H 3 C H 3 C H H 2 N H O H 3 C HN O O HO O P O O − N N III Co N N CH H 3 N N O OH H CH 3 CH 3 NH 2 O NH 2 = CH 2 Co III Ad Figure 11.1 Structure of vitamin B 12 cofactor. R R C C H vitamin B 12 C H C H OH OH H H* propanediol dehydrase vit B 12 *H H O + H 2 O *H CO 2 − SCoA methylmalonyl CoA mutase − O 2 C H* SCoA O vit B 12 O − O 2 C NH 3 CO 2 − glutamate mutase vit B 12 − O 2 C NH 3 CO 2 − Figure 11.2 Vitamin B 12 -dependent reactions.
242 Chapter 11 CH 2 Co III Ad H OH OH H H* CH 2 Co II Ad H OH OH CH 2 H* Co II Ad H H O OH CH 2 H* Co II Ad *H H O OH H H O H* CH 2 Ad Co II OH H OH H* CH 2 Co II Ad H OH OH *H CH 2 Co II Ad Figure 11.3 Mechanism for propanediol dehydrase. ates in the reaction by stopped Xow electron spin resonance (ESR) spectroscopy studies. The proposed mechanism for propanediol dehydrase is shown in Figure 11.3. Initiation of the reaction by homolysis of the carbon–cobalt bond generates an adenosyl radical, which abstracts the C-1 proS hydrogen, to give a substrate-derived radical. Migration of the OH group then occurs, from C-2 to C-1, probably through a cyclic transition state, to give a product radical. The reaction is completed by abstraction of H . from the 5 0 -deoxy-adenosyl group, and regeneration of the B 12 cofactor. The hydrate product is then dehydrated stereospeciWcally, losing the migrating hydroxyl group to give the product aldehyde. The methylmalonyl CoA mutase reaction is also initiated by formation of the 5 0 -deoxy-adenosyl radical. This abstracts a hydrogen atom from the substrate methyl group as shown in Figure 11.4. Intramolecular ring closure of this primary radical onto the thioester carbonyl forms a cyclopropyl-oxy radical intermediate. Fragmentation of this strained intermediate by cleavage of a diVerent C2C bond generates a more stable secondary radical adjacent to the carboxylate group. Attachment of the abstracted hydrogen atom gives the succinyl CoA product, and regenerates the vitamin B 12 cofactor. There is convincing precedent for this mechanism from organic reactions that perform this type of rearrangement via free radical intermediates. The X-ray crystal structure of methylmalonyl CoA mutase has been determined, and is shown in Figure 11.5. There are a small number of other vitamin B 12 -dependent rearrangements that can be also rationalised by the cyclisation of a radical intermediate onto an sp 2 carbon centre. The reaction catalysed by glutamate mutase, however, cannot be rationalised in this way, since the migrating group is an sp 3 centre, the a-carbon of glutamic acid. An alternative radical mechanism has been
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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
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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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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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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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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
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
Page 245 and 246: 234 Chapter 10 O H NH 3 CO 2 − CO
Page 247 and 248: 236 Chapter 10 sub-units. Each sub-
Page 249 and 250: 238 Chapter 10 Further reading Gene
Page 251: 11 Radicals in Enzyme Catalysis 11.
Page 255 and 256: 244 Chapter 11 − O 2 C − O CO
Page 257 and 258: 246 Chapter 11 H N H O 734 H N H PF
Page 259 and 260: 248 Chapter 11 H H* + H + H 3 N CO
Page 261 and 262: 250 Chapter 11 O HN NH + H 3 N H 3
Page 263 and 264: 252 Chapter 11 cofactor is involved
Page 265 and 266: 254 Chapter 11 Protein Radicals J.
Page 267 and 268: 256 Chapter 12 self-splicing reacti
Page 269 and 270: 258 Chapter 12 Figure 12.2 Structur
Page 271 and 272: 260 Chapter 12 antigen combining si
Page 273 and 274: 262 Chapter 12 R O OR' OH − R O
Page 275 and 276: 264 Chapter 12 CO 2 − − O 2 C O
Page 277 and 278: 266 Chapter 12 (1) Selective substr
Page 279 and 280: 268 Chapter 12 HO O HO OH HO OH O O
Page 281 and 282: 270 Chapter 12 Problems (1) How rev
Page 283 and 284: Appendix 1: Cahn-Ingold-Prelog Rule
Page 285 and 286: Appendix 2: Amino Acid Abbreviation
Page 287 and 288: 276 Appendix 3 Preparation of orang
Page 289 and 290: 278 Appendix 4 (2) Intramolecular a
Page 291 and 292: 280 Appendix 4 from water at a-posi
Page 293 and 294: 282 Appendix 4 Chapter 8 (1) Treat
Page 295 and 296: 284 Appendix 4 (b) Formation of rad
Page 297 and 298: 286 Index b-hydroxydecanoyl thioest
Page 299 and 300: 288 Index glycosylation 26-7 glysop
Page 301 and 302: 290 Index phenylalanine ammonia lya
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292 Index transition states 31-2 an
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