Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

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Enzymatic Hydrolysis and Group Transfer Reactions 91 His 159 His 159 Cys 25 Cys 25 Cys 25 Cys HN N H + HN NH S − S O R' NH NHR + NH 3 His 159 His 159 Cys Cys Cys 25 25 25 R'NH2 + N HN N HN N H H S H S O O - Gln O 17 NH H N H R' RNH + NHR NH 3 + NH 3 His 159 His 159 25 + HN NH N + HN H S NH S O - HO H N Gln 17 HO O Cys 25 NH 3 NHR + RNH + NH 3 Figure 5.9 Mechanism for papain. CAC His AGC Ser UGC Cys CAC His UGC Cys CAC His UCC Ser R S O X HN N H S R O X HN N H R O O X Figure 5.10 Possible evolution of serine proteases.
92 Chapter 5 now predominate Perhaps, as mentioned above, because they are more stable in an oxygen atmosphere. The metalloproteases The metalloproteases are characterised by a requirement for an active site metal ion, usually Zn 2þ , which is involved in the catalytic cycle. These enzymes can be readily distinguished from the other classes by treatment with metal chelating agents such as ethylene diamine tetra-acetic acid (EDTA) or 1,10-phenanthroline (see Figure 5.11), leading to removal of the metal ion cofactor and inactivation. The best characterised members of this family are carboxypeptidase A, a 307-amino acid exopeptidase from bovine pancreas which cleaves the C-terminal residue of a peptide chain (not arginine, lysine or proline); and thermolysin, a 35-kDa endopeptidase from Bacillus thermoproteolyticus which cleaves before hydrophobic amino acids such as leucine, isoleucine, valine or phenylalanine. Both enzymes contain a single Zn 2þ ion at their active sites, which in the resting state of the enzyme is co-ordinated by three protein ligands and one solvent water molecule. There is evidence to suggest that in both enzymes when the substrate is bound the water molecule is displaced by the carbonyl oxygen of the amide bond to be hydrolysed, which is thus activated towards nucleophilic attack by Zn 2þ Lewis acid catalysis. The mechanism of amide bond hydrolysis has been well studied in both enzymes, with slightly diVerent results emerging. Both enzymes contain an active site glutamate, which in theory could either act as a nucleophile to attack the amide carbonyl, or act as a base to deprotonate an attacking water molecule. In thermolysin the active site glutamate (Glu-143) is positioned 3.9 Å away from the amide carbonyl (see Figure 5.12a), too far away to act as a nucleophile, but far enough to accommodate an intervening water molecule, which is thought to be activated by co-ordination to the Zn 2þ cofactor. There is evidence from X-ray crystallography to suggest that Glu-143 acts as a base to deprotonate an attacking water molecule, forming an oxyanion intermediate which is stabilised by speciWc hydrogen bonds. Breakdown of this intermedi- O O N N − O O − M n+ − O − O O O N N M n+ Ethylene diamine tetra-acetic acid (EDTA) 1,10-Phenanthroline Figure 5.11 Metal chelating agents.
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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
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 +
Page 73 and 74: 62 Chapter 4 (2) by treatment with
Page 75 and 76: 64 Chapter 4 In general the stereoc
Page 77 and 78: H D T CO 2 H CO − 2 T HO D H −
Page 79 and 80: 68 Chapter 4 4.5 The existence of i
Page 81 and 82: 70 Chapter 4 18O 18O 18 O O P O −
Page 83 and 84: 72 Chapter 4 If a reaction involves
Page 85 and 86: 74 Chapter 4 O D H ketosteroid isom
Page 87 and 88: 76 Chapter 4 Table 4.3 Group speciW
Page 89 and 90: 78 Chapter 4 [S] (mM) Rate of produ
Page 91 and 92: 80 Chapter 4 Enzyme kinetics I.H. S
Page 93 and 94: 82 Chapter 5 O = C NHR peptidase H
Page 95 and 96: 84 Chapter 5 non-speciWc protease c
Page 97 and 98: 86 Chapter 5 His 57 His 57 Asp 102
Page 99 and 100: 88 Chapter 5 Other serine proteases
Page 101: 90 Chapter 5 Figure 5.8 Structure o
Page 105 and 106: OH R O Zn 2+ O O O Ph Glu 270 H 2 N
Page 107 and 108: 96 Chapter 5 CASE STUDY: HIV-1 prot
Page 109 and 110: 98 Chapter 5 HO Transition state pe
Page 111 and 112: 100 Chapter 5 The aminoacyl group o
Page 113 and 114: 102 Chapter 5 5.5 Enzymatic phospho
Page 115 and 116: 104 Chapter 5 Figure 5.29 Structure
Page 119 and 120: 108 Chapter 5 Adenosine 5 0 -tripho
Page 121 and 122: 110 Chapter 5 functional group. Gly
Page 123 and 124: 112 Chapter 5 CH 2 OH O RO HO OH O
Page 125 and 126: 114 Chapter 5 to these atoms that t
Page 127 and 128: 116 Chapter 5 Problems (1) Using pa
Page 129 and 130: 118 Chapter 5 (6) Retaining glycosi
Page 131 and 132: 120 Chapter 5 J.R. Knowles (1980) E
Page 133 and 134: 122 Chapter 6 +1.0 Redox potential
Page 135 and 136: Table 6.1 Classes of redox enzymes.
Page 137 and 138: 126 Chapter 6 An important point is
Page 139 and 140: 128 Chapter 6 O H − OH − O OH H
Page 141 and 142: 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 149 and 150: 138 Chapter 6 (a) (b) Figure 6.23 S
Page 151 and 152: 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 +
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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
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290 Index phenylalanine ammonia lya
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292 Index transition states 31-2 an
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