Structure and mechanism in protein science: a guide to enzyme catalysis and protein folding
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
New York
Freeman
2000
|
| Ausgabe: | 3. print. |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | Früher u.d.T.: Ferst, Alan: Enzyme structure and mechanism |
| Beschreibung: | XXI, 631 S. Ill., graph. Darst. |
| ISBN: | 0716732688 |
Internformat
MARC
| LEADER | 00000nam a2200000 c 4500 | ||
|---|---|---|---|
| 001 | BV013524001 | ||
| 003 | DE-604 | ||
| 005 | 20010119 | ||
| 007 | t | ||
| 008 | 010109s2000 ad|| |||| 00||| eng d | ||
| 020 | |a 0716732688 |9 0-7167-3268-8 | ||
| 035 | |a (OCoLC)249590431 | ||
| 035 | |a (DE-599)BVBBV013524001 | ||
| 040 | |a DE-604 |b ger |e rakwb | ||
| 041 | 0 | |a eng | |
| 049 | |a DE-M49 |a DE-29T | ||
| 082 | 0 | |a 572.6 | |
| 082 | 0 | |a 547/.75 | |
| 084 | |a WD 5050 |0 (DE-625)148185: |2 rvk | ||
| 084 | |a CHE 829f |2 stub | ||
| 084 | |a CHE 827f |2 stub | ||
| 100 | 1 | |a Fersht, Alan |d 1943- |e Verfasser |4 aut | |
| 245 | 1 | 0 | |a Structure and mechanism in protein science |b a guide to enzyme catalysis and protein folding |c Alan Fersht |
| 250 | |a 3. print. | ||
| 264 | 1 | |a New York |b Freeman |c 2000 | |
| 300 | |a XXI, 631 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 500 | |a Früher u.d.T.: Ferst, Alan: Enzyme structure and mechanism | ||
| 650 | 0 | 7 | |a Enzymkinetik |0 (DE-588)4133166-7 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Proteinfaltung |0 (DE-588)4324567-5 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Katalyse |0 (DE-588)4029921-1 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Chemische Struktur |0 (DE-588)4009857-6 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Proteine |0 (DE-588)4076388-2 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Enzym |0 (DE-588)4014988-2 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Enzymkatalyse |0 (DE-588)4152480-9 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Reaktionsmechanismus |0 (DE-588)4177123-0 |2 gnd |9 rswk-swf |
| 689 | 0 | 0 | |a Enzym |0 (DE-588)4014988-2 |D s |
| 689 | 0 | 1 | |a Chemische Struktur |0 (DE-588)4009857-6 |D s |
| 689 | 0 | |5 DE-604 | |
| 689 | 1 | 0 | |a Enzym |0 (DE-588)4014988-2 |D s |
| 689 | 1 | 1 | |a Reaktionsmechanismus |0 (DE-588)4177123-0 |D s |
| 689 | 1 | |5 DE-604 | |
| 689 | 2 | 0 | |a Proteinfaltung |0 (DE-588)4324567-5 |D s |
| 689 | 2 | 1 | |a Enzymkatalyse |0 (DE-588)4152480-9 |D s |
| 689 | 2 | |5 DE-604 | |
| 689 | 3 | 0 | |a Enzym |0 (DE-588)4014988-2 |D s |
| 689 | 3 | 1 | |a Katalyse |0 (DE-588)4029921-1 |D s |
| 689 | 3 | 2 | |a Proteine |0 (DE-588)4076388-2 |D s |
| 689 | 3 | 3 | |a Enzymkinetik |0 (DE-588)4133166-7 |D s |
| 689 | 3 | |8 1\p |5 DE-604 | |
| 689 | 4 | 0 | |a Enzymkatalyse |0 (DE-588)4152480-9 |D s |
| 689 | 4 | 1 | |a Proteine |0 (DE-588)4076388-2 |D s |
| 689 | 4 | 2 | |a Enzymkinetik |0 (DE-588)4133166-7 |D s |
| 689 | 4 | |8 2\p |5 DE-604 | |
| 856 | 4 | 2 | |m HBZ Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009231128&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-009231128 | ||
| 883 | 1 | |8 1\p |a cgwrk |d 20201028 |q DE-101 |u https://d-nb.info/provenance/plan#cgwrk | |
| 883 | 1 | |8 2\p |a cgwrk |d 20201028 |q DE-101 |u https://d-nb.info/provenance/plan#cgwrk | |
Datensatz im Suchindex
| _version_ | 1804128316580429824 |
|---|---|
| adam_text | Titel: Structure and mechanism in protein science
Autor: Fersht, Alan
Jahr: 2000
CONTENTS
Preface xx
1. The Three-Dimensional Structure of Proteins 1
A. The primary structure of proteins 3
B. Methods for determination of three-dimensional structure 4
1. Structures of crystalline proteins by x-ray diffraction methods 4
2. Neutron diffraction 6
3. Structure of proteins in solution from NMR methods 7
C. The three-dimensional structure of proteins 8
1. The structural building blocks 9
2. The Ramachandran diagram 14
3. Motifs or supersecondary structures 20
4. Assembly of proteins from the building blocks 22
D. Protein diversity 25
1. Introns, exons, and inteins and exteins 25
2. Divergent evolution of families of proteins 26
3. Convergent evolution 28
4. Convergence or divergence? 30
5. a//3 Barrel (or TIM barrel) proteins 30
6. Dehydrogenases and domains 32
7. Evolution of proteins by fusion of gene fragments 32
8. Homology, sequence identity, and structural similarity 33
E. Higher levels of organization: Multienzyme complexes 34
1. Multiheaded enzymes and the noncovalent association
of different activities 35
2. The arom complex 36
3. The pyruvate dehydrogenase complex 37
4. DNA polymerases 37
5. Reasons for multiple activities and multienzyme complexes 38
F. The structure of enzyme-substrate complexes 38
1. Methods for examining stable enzyme-substrate complexes 39
2. Example 1: The serine proteases 40
3. Example 2: Lysozyme 43
v
vi CONTENTS
G. Flexibility and conformational mobility of proteins 44
1. Are the crystal and solution structures of an enzyme
essentially identical? 45
2. Modes of motion and flexibility observed in proteins 46
3. Protein mobility and enzyme mechanism 50
2. Chemical Catalysis 54
A. Transition state theory 54
1. The significance and the application of transition
state theory 57
2. The Hammond postulate 57
3. Chemical basis of the Hammond postulate 58
B. Principles of catalysis 59
1. Where, why, and how catalysis is required 59
2. General-acid-base catalysis 62
3. Intramolecular catalysis: The effective concentration
of a group on an enzyme 65
4. Entropy: The theoretical basis of intramolecular catalysis
and effective concentration 68
5. Orbital steering 72
6. Electrostatic catalysis 73
7. Metal ion catalysis 74
C. Covalent catalysis 77
1. Electrophilic catalysis by Schiff base formation 77
2. Pyridoxal phosphate—Electrophilic catalysis 79
3. Thiamine pyrophosphate—Electrophilic catalysis 82
4. Nucleophilic catalysis 84
D. Structure-activity relationships 85
1. Nucleophilic attack at the carbonyl group 86
2. Factors determining nucleophilicity and leaving
group ability 88
E. The principle of microscopic reversibility or detailed balance 93
F. The principle of kinetic equivalence 94
G. Kinetic isotope effects 96
1. Primary isotope effects 96
2. Multiple isotope effects 98
3. Secondary isotope effects 98
4. Solvent isotope effects 99
H. Summary of classical factors of enzyme catalysis 100
CONTENTS vii
3. The Basic Equations of Enzyme Kinetics 103
A. Steady state kinetics 103
1. The experimental basis: The Michaelis-Menten equation 104
2. Interpretation of the kinetic phenomena for single-substrate
reactions: The Michaelis-Menten mechanism 105
3. Extensions and modifications of the Michaelis-Menten
mechanism 106
B. The significance of the Michaelis-Menten parameters 108
1. The meaning of £cat: The catalytic constant 108
2. The meaning of Ku: Real and apparent equilibrium constants 109
3. The meaning of kcat/Ku: The specificity constant 110
C. Graphical representation of data 111
D. Inhibition 112
1. Competitive inhibition 113
2. Noncompetitive, uncompetitive, and mixed inhibition 113
E. Nonproductive binding 114
F. KJKM = k2IKs 116
G. Competing substrates 116
1. An alternative formulation of the Michaelis-Menten equation 116
2. Specificity for competing substrates 117
H. Reversibility: The Haldane equation 117
1. Equilibria in solution 117
2. Equilibria on the enzyme surface (internal equilibria) 118
I. Breakdown of the Michaelis-Menten equation 119
J. Multisubstrate systems 119
1. The random sequential mechanism 120
2. The ordered mechanism 120
3. The Theorell-Chance mechanism 120
4. The ping-pong (or substituted-enzyme or
double-displacement) mechanism 120
K. Useful kinetic shortcuts 122
1. Calculation of net rate constants 122
2. Use of transit times instead of rate constants 123
L. Thermodynamic cycles 125
1. Basic thermodynamic cycles 125
2. Two ligands or substrates binding to an enzyme 126
3. Linked ionization and equilibria: Microscopic and
macroscopic constants 127
viii CONTENTS
4. Hypothetical steps: Mutations 129
5. Double mutant cycles 129
4. Measurement and Maqnitude of Individual
Rate Constants 132
A. Rapid mixing and sampling techniques 133
1. The continuous-flow method 133
2. The stopped-flow method 134
3. Rapid quenching techniques 135
B. Flash photolysis 136
C. Relaxation methods 137
1. Temperature jump 137
2. Nuclear magnetic resonance 138
D. Analysis of pre- steady state and relaxation kinetics 139
1. Simple exponentials 139
2. Association of enzyme and substrate 143
3. Consecutive reactions 143
4. Parallel reactions 149
5. Derivation of equations for temperature jump 149
6. A general solution of two-step consecutive reversible reactions 150
7. Experimental application of pre-steady state kinetics 153
E. The absolute concentration of enzymes 155
1. Active-site titration and the magnitudes of bursts 155
2. The dependence of the burst on substrate concentration 156
3. Active-site titration versus rate assay 158
miH33BB!S9S^S9iiiiiiH^^^I 158
A. Upper limits on rate constants 158
1. Association and dissociation 158
2. Chemical processes 162
3. Proton transfers 162
B. Enzymatic rate constants and rate-determining processes 164
1. Association of enzymes and substrates 164
2. Association can be rate-determining for KJKM 166
3. Dissociation of enzyme-substrate and enzyme-product
complexes 167
4. Enzyme-product release can be rate-determining for fccat 167
5. Conformational changes 167
CONTENTS ix
5. The pH Dependence of Enzyme Catalysis 169
A. Ionization of simple acids and bases: The basic equations 169
1. Extraction of p^ s by inspection of equations 173
B. The effect of ionizations of groups in enzymes on kinetics 173
1. The simple theory: The Michaelis-Menten mechanism 174
2. The pH dependence of £cat, kcJKM, KM, and IKM 174
3. A simple rule for the prediction and assignment of pA^ s 175
C. Modifications and breakdown of the simple theory 176
1. Modifications due to additional intermediates 176
2. Breakdown of the simple rules: Briggs-Haldane kinetics
and change of rate-determining step with pH: Kinetic pATa s 178
3. An experimental distinction between kinetic and
equilibrium PjSTq s 179
4. Microscopic and macroscopic p^ s 179
D. The influence of surface charge on p/fa s of groups in enzymes 179
E. Graphical representation of data 181
F. Illustrative examples and experimental evidence 182
1. The pKa of the active site of chymotrypsin 183
G. Direct titration of groups in enzymes 184
1. The effect of D2O on pH/pD and pKa s 185
2. Methods 185
H. The effect of temperature, polarity of solvent, and ionic
strength on p2STa s of groups in enzymes and in solution 187
I. Highly perturbed pKa s in enzymes 188
6. Practical Methods for Kinetics and Equilibria 191
A. Spectrometry and methods for kinetics 191
1. Spectrophotometry 191
2. Spectrofluorimetry 192
3. Circular dichroism 193
4. Automated spectrophotometric and spectrofluorimetric
procedures 195
5. Coupled assays 196
6. Automatic titration of acid or base 196
7. Radioactive procedures 196
8. Label-free optical detection 199
B. Plotting kinetic data 199
1. Exponentials 199
2. Second-order reactions 200
3. Michaelis-Menten kinetics 201
x CONTENTS
C. Determination of protein-ligand dissociation constants 202
1. Kinetics 202
2. Equilibrium dialysis 202
3. Equilibrium gel filtration 203
4. Ultracentrifugation 204
5. Filter assays 205
6. Spectroscopic methods 205
7. Stoichiometric titration 206
8. Microcalorimetry 207
D. Plotting binding data 207
1. The single binding site 207
2. Multiple binding sites 208
E. Computer fitting of data 209
F. Statistics, errors of observation, and accuracy 209
1. Normal or Gaussian distribution 210
2. Errors in sampling 210
3. Combining errors of measurement 211
4. Poisson distribution 212
5. Signal to noise in absorbance, circular dichroism,
fluorescence, and radioactive counting 212
Appendix: Measurement of protein concentration 214
7. Detection of Intermediates in Enzymatic Reactions 216
A. Pre-steady state versus steady state kinetics 216
1. Detection of intermediates: What is proof ? 217
B. Chymotrypsin: Detection of intermediates by stopped-flow
spectrophotometry, steady state kinetics, and
product partitioning 218
1. Detection of intermediates from a burst of product release 218
2. Proof of formation of an intermediate from pre-steady
state kinetics under single-turnover conditions 219
3. Detection of the acylenzyme in the hydrolysis of esters
by steady state kinetics and partitioning experiments 223
4. Detection of the acylenzyme in the hydrolysis of amides and
peptides 229
5. The validity of partitioning experiments and some possible
experimental errors 230
C. Further examples of detection of intermediates
by partition and kinetic experiments 231
1. Alkaline phosphatase 231
CONTENTS xi
2. Acid phosphatase 233
3. )3-Galactosidase 233
D. Aminoacyl-tRNA synthetases: Detection of intermediates
by quenched flow, steady state kinetics, and isotope exchange 235
1. The reaction mechanism 235
2. The editing mechanism 239
E. Detection of conformational changes 242
F. The future 242
8. Stereochemistry of Enzymatic Reactions 245
A. Optical activity and chirality 245
1. Notation 246
2. Differences between the stereochemistries of enzymatic and
nonenzymatic reactions 247
3. Conformation and configuration 249
B. Examples of stereospecific enzymatic reactions 249
1. NAD+-and NADP+-dependent oxidation and reduction 249
2. Stereochemistry of the fumarase-catalyzed hydration
of fumarate 250
3. Demonstration that the enediol intermediate in aldose-ketose
isomerase reactions is syn 251
4. Use of locked substrates to determine the anomeric
specificity of phosphofructokinase 252
C. Detection of intermediates from retention or inversion
of configuration at chiral centers 253
1. Stereochemistry of nucleophilic reactions 253
2. The validity of stereochemical arguments 254
3. Intermediates in reactions of lysozyme and /3-galactosidase 255
D. The chiral methyl group 255
1. The fundamental difference between generating a chiral
methyl group from a methylene group and converting a
chiral methyl group into methylene 256
2. The chirality assay 256
3. Stereochemistry of the malate synthase reaction 258
E. Chiral phosphate 259
1. A preview of phosphoryl transfer chemistry 259
2. Chirality of phosphoryl derivatives 260
3. Examples of chiral phosphoryl transfer 262
4. Positional isotope exchange 265
5. A summary of the stereochemistry of enzymatic phosphoryl
transfers 266
xii CONTENTS
F. Stereoelectronic control of enzymatic reactions 266
1. Pyridoxal phosphate reactivity 267
2. Stereoelectronic effects in reactions of proteases 270
9. Active-Site-Directed and Enzyme-Activated
Irreversible Inhibitors: Affinity Labels and
Suicide Inhibitors 273
A. Chemical modification of proteins 273
1. The chemical reactivity of amino acid side chains 276
B. Active-site-directed irreversible inhibitors 277
C. Enzyme-activated irreversible inhibitors 280
1. Pyridoxal phosphate-linked enzymes 284
2. Monoamine oxidases and flavoproteins 285
D. Slow, tight-binding inhibition 286
1. Kinetics of slow, tight-binding inhibition 286
10. Conformational Chanqe, Allosteric Regulation,
Motors, and Work 289
A. Positive cooperativity 289
B. Mechanisms of allosteric interactions and cooperativity 291
1. The Monod-Wyman-Changeux (MWC) concerted
mechanism 292
2. The Koshland-Nemethy-Filmer (KNF) sequential model 295
3. The general model 296
4. Nested cooperativity 296
C. Negative cooperativity and half-of-the-sites reactivity 296
D. Quantitative analysis of cooperativity 297
1. The Hill equation: A measure of cooperativity 297
2. The MWC binding curve 300
3. The KNF binding curve 303
4. Diagnostic tests for cooperativity; and MWC versus KNF
mechanisms 303
E. Molecular mechanism of cooperative binding to hemoglobin 304
1. The physiological importance of the cooperative binding
of oxygen 304
2. Atomic events in the oxygenation of hemoglobin 304
3. Chemical models of hemes 307
F. Regulation of metabolic pathways 308
CONTENTS xiii
G. Phosphofructokinase and control by allosteric feedback 309
1. The structure of the R state 311
2. The structure of the T state 311
H. Glycogen phosphorylase and control by phosphorylation 312
1. Glycogen phosphorylase and regulation of glycogenolysis 312
2. The allosteric activation of phosphorylases 314
I. G proteins: Molecular switches 315
J. Motor proteins 317
K. ATP synthesis by rotary catalysis: ATP synthase and
FrATPase 318
11. Forces Between Molecules, and Binding Energies 324
A. Interactions between nonbonded atoms 325
1. Electrostatic interactions 325
2. Nonpolar interactions (van der Waals or dispersion forces) 327
3. The hydrogen bond 329
4. Force fields for simulating energies in proteins and
complexes 331
B. The binding energies of proteins and ligands 332
1. The hydrophobic bond 332
2. Hydrogen bonds, salt bridges and the hydrogen bond
inventory 337
C. Experimental measurements of incremental energies 339
1. Binding versus specificity 339
2. Estimation of increments in binding energy from kinetics 340
D. Entropy and binding 345
E. Enthalpy-entropy compensation 346
F. Summary 347
12. Enzyme—Substrate Complementarity and
the Use of Binding Energy in Catalysis 349
A. Utilization of enzyme-substrate binding energy
in catalysis 350
1. Binding energy lowers the activation energy of kcat/KM 350
2. Interconversion of binding and chemical activation energies 350
3. Enzyme complementarity to transition state implies that
k^JKu is at a maximum 354
xiv CONTENTS
B. Experimental evidence for the utilization of binding energy
in catalysis and enzyme-transition state complementarity 356
1. Classic experiments: Structure-activity relationships
of modified substrates 356
2. Transition state analogues: Probes of complementarity 356
3. Catalytic antibodies (abzymes) 361
4. Structure-activity experiments on engineered enzymes 362
C. Evolution of the maximum rate: Strong binding of the
transition state and weak binding of the substrate 362
1. The principle of maximization of KM at constant kC!itIKM 363
2. Experimental observations on KM s 364
3. The perfectly evolved enzyme for maximum rate 368
D. Molecular mechanisms for the utilization of binding energy 368
1. Strain 369
2. Induced fit 369
3. Nonproductive binding 371
4. The unimportance of strain, induced fit, and nonproductive
binding in specificity 372
5. Strain, induced fit, nonproductive binding, and steady
state kinetics 372
6. Conclusions about the nature of strain: Strain or stress? 372
E. Effects of rate optimization on accumulation
of intermediates and internal equilibria in enzymes 374
1. Accumulation of intermediates 374
2. Balanced internal equilibria 375
13. Specificity and Editing Mechanisms 377
A. Limits on specificity 378
1. Michaelis-Menten kinetics 380
2. The general case 381
3. Interacting active sites 382
4. The stereochemical origin of specificity 383
B. Editing or proofreading mechanisms 384
1. Editing in protein synthesis 385
2. Editing in DNA replication 389
C. The cost of accuracy 395
1. The cost-selectivity equation for editing mechanisms 395
2. Single-feature recognition:/ = / / 397
3. Double-feature recognition: / / / 399
CONTENTS xv
14. Recombinant DNA Technoloqy 401
A. The structure and properties of DNA 401
1. DNA may be replicated: DNA polymerases 404
2. Gaps in DNA may be sealed: DNA ligases 405
3. Duplex DNA may be cleaved at specific sequences:
Restriction endonucleases 406
4. DNA fragments may be joined by using enzymes 407
5. Joining DNA by complementary homopolymeric tails:
Terminal transferase 408
6. Amplifying DNA by the polymerase chain reaction (PCR) 408
7. Processive versus distributive polymerization 410
B. Cloning enzyme genes for overproduction 410
1. Vectors 412
2. Screening 412
C. Site-specific mutagenesis for rational design 413
D. Random mutagenesis and repertoire selection 415
1. Random mutagenesis 415
2. Repertoire selection: Phage display 416
15. Protein Engineering 420
¦HoKfflfflfiiBfflisiHIilHIIHi 420
A. Mechanistic goals 421
B. The tyrosyl-tRNA synthetase 422
C. Requirements for systematic site-directed mutagenesis
studies 423
1. Active-site titration 423
2. Pre-steady state kinetics 424
3. Starting point: The crystal structure of the E • Tyr-AMP
complex 424
D. Choice of mutation 425
E. Strategy: Free energy profiles and difference energy
diagrams 427
F. Results from difference energy diagrams for the activation
oftyrosine 428
1. Demonstration of enzyme-transition state complementarity 428
xvi CONTENTS
2. Discovery of enzyme-intermediate complementarity:
Balancing internal equilibrium constants; sequestration
of unstable intermediates 430
3. Detection of an induced-fit process 432
4. The catalytic mechanism for activation of tyrosine 432
5. Mechanism of transfer step 435
G. Relationship between apparent binding energies
from difference energies and incremental binding energies 435
H. Probing evolution: Reverse genetics 438
1. Differential and uniform binding changes 438
2. Fine-tuning activity of tyrosyl-tRNA synthetase toward [ATP] 439
3. Optimizing rate in a multistep reaction 440
I. Linear free energy relationships in binding energies 442
J. Probing the gross structure and symmetry of the enzyme
by mutagenesis 444
1. Domain structure of the enzyme 445
2. Construction of heterodimers 446
K. Measuring the free energy of hydrolysis of Tyr-AMP 449
A. Subtilisin 450
B. Dissection of the catalytic triad and the oxyanion
binding site 450
C. Redesigning specificity 452
1. Subsites 452
2. Subtiloligase 453
D. Engineering of stability and other properties 454
16. Case Studies of Enzyme Structure and Mechanism 457
A. The dehydrogenases 458
1. The alcohol dehydrogenases 460
2. L-Lactate and L-malate dehydrogenases 465
3. Glyceraldehyde 3-phosphate dehydrogenase 469
4. Some generalizations about dehydrogenases 472
B. The proteases 472
1. The serine proteases 473 )
2. The cysteine proteases 482
3. The zinc proteases 482
4. The carboxyl (aspartyl) proteases 486
CONTENTS xvii
C. Ribonucleases 491
1. The structure of ribonuclease A and its complexes 493
2. Mechanism of barnase 495
D. Lysozyme 497
1. The oxocarbenium ion 498
2. Electrostatic and general-acid catalysis 498
3. Binding energies of the subsites 499
E. Some generalizations 500
17. Protein Stability 508
A. Protein denaturation 509
1. Thermodynamics of protein folding 509
2. Solvent denaturation 513
3. Acid-or base-induced denaturation 516
4. Two-state versus multistate transitions 517
B. Structure of the denatured state 518
1. The denatured state under denaturing conditions, U 520
2. The denatured state at physiological conditions, DPhys 520
3. First-and second-order transitions 521
C. Measurement of changes in stability 522
1. Thermal denaturation 522
2. Solvent denaturation 522
D. Energetics of formation of structure 523
1. a Helixes 523
2. /3-Sheet propensities 532
3. The hydrophobic core 532
4. Disulfide crosslinks 534
5. Relationship between statistical surveys and
measured energetics 535
6. Additivity of binding energy changes 535
E. Stability-activity tradeoff? 536
F. Prediction of three-dimensional structure
from primary structure 536
18. Kinetics of Protein Folding 540
A. Kinetics of folding 541
1. Basic methods 541
2. Multiple phases and cw-peptidyl-prolyl bonds 541
xviii CONTENTS
B. Two-state kinetics 543
1. Effects of denaturant on unfolding and folding kinetics 543
2. Interpretation of the rate laws for denaturation and folding:
The Tanford /3 value 544
3. Effects of temperature on folding 545
4. Two-state kinetics and intermediates 547
5. Kinetics tests for intermediates 547
C. Multistate kinetics 553
1. Are intermediates on or off pathway? 553
D. Transition states in protein folding 556
1. What is a transition state in protein folding? 557
2. Can we apply transition state theory? 558
E. Introduction to -value analysis 558
1. Changes in energy levels on mutation 559
2. Choice of mutations: Nondisruptive deletions 560
3. Relationship between f and the Br0nsted /3 562
4. Fractional values of $ 562
5. Benchmarking of simulations with 563
F. ^^H-exehange methods 563
1. H/2H-exchange at equilibrium 563
2. Exchange at equilibrium cannot be used to determine
pathways 566
3. Uses of equilibrium H^H-exchange in folding studies 567
4. Quenched-flow !H/2H-exchange 567
5. analysis versus quenched-flow H/2H-exchange 568
G. Folding of peptides 569
1. Loops 569
2. a Helixes 569
3. /3 Hairpin 570
4. Very fast folding small proteins 570
19. Folding Pathways and Energy Landscapes 573
A. Levinthal s paradox 575
B. Folding of CI2 576
1. Structure of the native protein 576
2. Folding kinetics 577
3. Structures of peptide fragments 577
4. Structure of the denatured protein 578
5. Structure of the transition state 578
6. Molecular dynamics simulations of the transition state 583
CONTENTS xix
C. The nucleation-condensation mechanism 583
1. The lessons from CI2 folding 583
2. The nucleation-condensation (or -collapse) mechanism 585
3. Direct evidence for nucleation-condensation in assembly
of protein fragments 587
D. Folding of barnase 588
1. Structure of the native protein 588
2. Folding kinetics 589
3. Structures of peptide fragments 589
4. Structure of the denatured protein 589
5. Structures of the intermediate and transition state
for unfolding 590
6. Molecular dynamics, , and NMR conspire to
describe the folding pathway 591
E. Folding pathway of barstar at microsecond resolution 591
F. Unified folding scheme? 593
G. Insights from theory 597
1. Lattice simulations 597
2. Spin glass theory and other abstract methods 598
3. The folding funnel 598
H. Optimization of folding rates 600
1. Factors that determine rate constants for two-state folding 601
I. Molecular chaperones 603
1. Chaperones and heat-shock proteins 603
2. GroEL(Hsp60orCpn60) 604
3. A real folding funnel 611
Index 615
|
| any_adam_object | 1 |
| author | Fersht, Alan 1943- |
| author_facet | Fersht, Alan 1943- |
| author_role | aut |
| author_sort | Fersht, Alan 1943- |
| author_variant | a f af |
| building | Verbundindex |
| bvnumber | BV013524001 |
| classification_rvk | WD 5050 |
| classification_tum | CHE 829f CHE 827f |
| ctrlnum | (OCoLC)249590431 (DE-599)BVBBV013524001 |
| dewey-full | 572.6 547/.75 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 572 - Biochemistry 547 - Organic chemistry |
| dewey-raw | 572.6 547/.75 |
| dewey-search | 572.6 547/.75 |
| dewey-sort | 3572.6 |
| dewey-tens | 570 - Biology 540 - Chemistry and allied sciences |
| discipline | Chemie / Pharmazie Biologie Chemie |
| edition | 3. print. |
| format | Book |
| fullrecord | <?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>02723nam a2200685 c 4500</leader><controlfield tag="001">BV013524001</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">20010119 </controlfield><controlfield tag="007">t</controlfield><controlfield tag="008">010109s2000 ad|| |||| 00||| eng d</controlfield><datafield tag="020" ind1=" " ind2=" "><subfield code="a">0716732688</subfield><subfield code="9">0-7167-3268-8</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)249590431</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)BVBBV013524001</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-604</subfield><subfield code="b">ger</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1="0" ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="049" ind1=" " ind2=" "><subfield code="a">DE-M49</subfield><subfield code="a">DE-29T</subfield></datafield><datafield tag="082" ind1="0" ind2=" "><subfield code="a">572.6</subfield></datafield><datafield tag="082" ind1="0" ind2=" "><subfield code="a">547/.75</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">WD 5050</subfield><subfield code="0">(DE-625)148185:</subfield><subfield code="2">rvk</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">CHE 829f</subfield><subfield code="2">stub</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">CHE 827f</subfield><subfield code="2">stub</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Fersht, Alan</subfield><subfield code="d">1943-</subfield><subfield code="e">Verfasser</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Structure and mechanism in protein science</subfield><subfield code="b">a guide to enzyme catalysis and protein folding</subfield><subfield code="c">Alan Fersht</subfield></datafield><datafield tag="250" ind1=" " ind2=" "><subfield code="a">3. print.</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">New York</subfield><subfield code="b">Freeman</subfield><subfield code="c">2000</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">XXI, 631 S.</subfield><subfield code="b">Ill., graph. Darst.</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">Früher u.d.T.: Ferst, Alan: Enzyme structure and mechanism</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Enzymkinetik</subfield><subfield code="0">(DE-588)4133166-7</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Proteinfaltung</subfield><subfield code="0">(DE-588)4324567-5</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Katalyse</subfield><subfield code="0">(DE-588)4029921-1</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Chemische Struktur</subfield><subfield code="0">(DE-588)4009857-6</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Proteine</subfield><subfield code="0">(DE-588)4076388-2</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Enzym</subfield><subfield code="0">(DE-588)4014988-2</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Enzymkatalyse</subfield><subfield code="0">(DE-588)4152480-9</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Reaktionsmechanismus</subfield><subfield code="0">(DE-588)4177123-0</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="689" ind1="0" ind2="0"><subfield code="a">Enzym</subfield><subfield code="0">(DE-588)4014988-2</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2="1"><subfield code="a">Chemische Struktur</subfield><subfield code="0">(DE-588)4009857-6</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2=" "><subfield code="5">DE-604</subfield></datafield><datafield tag="689" ind1="1" ind2="0"><subfield code="a">Enzym</subfield><subfield code="0">(DE-588)4014988-2</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="1" ind2="1"><subfield code="a">Reaktionsmechanismus</subfield><subfield code="0">(DE-588)4177123-0</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="1" ind2=" "><subfield code="5">DE-604</subfield></datafield><datafield tag="689" ind1="2" ind2="0"><subfield code="a">Proteinfaltung</subfield><subfield code="0">(DE-588)4324567-5</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="2" ind2="1"><subfield code="a">Enzymkatalyse</subfield><subfield code="0">(DE-588)4152480-9</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="2" ind2=" "><subfield code="5">DE-604</subfield></datafield><datafield tag="689" ind1="3" ind2="0"><subfield code="a">Enzym</subfield><subfield code="0">(DE-588)4014988-2</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="3" ind2="1"><subfield code="a">Katalyse</subfield><subfield code="0">(DE-588)4029921-1</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="3" ind2="2"><subfield code="a">Proteine</subfield><subfield code="0">(DE-588)4076388-2</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="3" ind2="3"><subfield code="a">Enzymkinetik</subfield><subfield code="0">(DE-588)4133166-7</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="3" ind2=" "><subfield code="8">1\p</subfield><subfield code="5">DE-604</subfield></datafield><datafield tag="689" ind1="4" ind2="0"><subfield code="a">Enzymkatalyse</subfield><subfield code="0">(DE-588)4152480-9</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="4" ind2="1"><subfield code="a">Proteine</subfield><subfield code="0">(DE-588)4076388-2</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="4" ind2="2"><subfield code="a">Enzymkinetik</subfield><subfield code="0">(DE-588)4133166-7</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="4" ind2=" "><subfield code="8">2\p</subfield><subfield code="5">DE-604</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">HBZ Datenaustausch</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009231128&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="999" ind1=" " ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-009231128</subfield></datafield><datafield tag="883" ind1="1" ind2=" "><subfield code="8">1\p</subfield><subfield code="a">cgwrk</subfield><subfield code="d">20201028</subfield><subfield code="q">DE-101</subfield><subfield code="u">https://d-nb.info/provenance/plan#cgwrk</subfield></datafield><datafield tag="883" ind1="1" ind2=" "><subfield code="8">2\p</subfield><subfield code="a">cgwrk</subfield><subfield code="d">20201028</subfield><subfield code="q">DE-101</subfield><subfield code="u">https://d-nb.info/provenance/plan#cgwrk</subfield></datafield></record></collection> |
| id | DE-604.BV013524001 |
| illustrated | Illustrated |
| indexdate | 2024-07-09T18:47:18Z |
| institution | BVB |
| isbn | 0716732688 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-009231128 |
| oclc_num | 249590431 |
| open_access_boolean | |
| owner | DE-M49 DE-BY-TUM DE-29T |
| owner_facet | DE-M49 DE-BY-TUM DE-29T |
| physical | XXI, 631 S. Ill., graph. Darst. |
| publishDate | 2000 |
| publishDateSearch | 2000 |
| publishDateSort | 2000 |
| publisher | Freeman |
| record_format | marc |
| spelling | Fersht, Alan 1943- Verfasser aut Structure and mechanism in protein science a guide to enzyme catalysis and protein folding Alan Fersht 3. print. New York Freeman 2000 XXI, 631 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Früher u.d.T.: Ferst, Alan: Enzyme structure and mechanism Enzymkinetik (DE-588)4133166-7 gnd rswk-swf Proteinfaltung (DE-588)4324567-5 gnd rswk-swf Katalyse (DE-588)4029921-1 gnd rswk-swf Chemische Struktur (DE-588)4009857-6 gnd rswk-swf Proteine (DE-588)4076388-2 gnd rswk-swf Enzym (DE-588)4014988-2 gnd rswk-swf Enzymkatalyse (DE-588)4152480-9 gnd rswk-swf Reaktionsmechanismus (DE-588)4177123-0 gnd rswk-swf Enzym (DE-588)4014988-2 s Chemische Struktur (DE-588)4009857-6 s DE-604 Reaktionsmechanismus (DE-588)4177123-0 s Proteinfaltung (DE-588)4324567-5 s Enzymkatalyse (DE-588)4152480-9 s Katalyse (DE-588)4029921-1 s Proteine (DE-588)4076388-2 s Enzymkinetik (DE-588)4133166-7 s 1\p DE-604 2\p DE-604 HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009231128&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 2\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk |
| spellingShingle | Fersht, Alan 1943- Structure and mechanism in protein science a guide to enzyme catalysis and protein folding Enzymkinetik (DE-588)4133166-7 gnd Proteinfaltung (DE-588)4324567-5 gnd Katalyse (DE-588)4029921-1 gnd Chemische Struktur (DE-588)4009857-6 gnd Proteine (DE-588)4076388-2 gnd Enzym (DE-588)4014988-2 gnd Enzymkatalyse (DE-588)4152480-9 gnd Reaktionsmechanismus (DE-588)4177123-0 gnd |
| subject_GND | (DE-588)4133166-7 (DE-588)4324567-5 (DE-588)4029921-1 (DE-588)4009857-6 (DE-588)4076388-2 (DE-588)4014988-2 (DE-588)4152480-9 (DE-588)4177123-0 |
| title | Structure and mechanism in protein science a guide to enzyme catalysis and protein folding |
| title_auth | Structure and mechanism in protein science a guide to enzyme catalysis and protein folding |
| title_exact_search | Structure and mechanism in protein science a guide to enzyme catalysis and protein folding |
| title_full | Structure and mechanism in protein science a guide to enzyme catalysis and protein folding Alan Fersht |
| title_fullStr | Structure and mechanism in protein science a guide to enzyme catalysis and protein folding Alan Fersht |
| title_full_unstemmed | Structure and mechanism in protein science a guide to enzyme catalysis and protein folding Alan Fersht |
| title_short | Structure and mechanism in protein science |
| title_sort | structure and mechanism in protein science a guide to enzyme catalysis and protein folding |
| title_sub | a guide to enzyme catalysis and protein folding |
| topic | Enzymkinetik (DE-588)4133166-7 gnd Proteinfaltung (DE-588)4324567-5 gnd Katalyse (DE-588)4029921-1 gnd Chemische Struktur (DE-588)4009857-6 gnd Proteine (DE-588)4076388-2 gnd Enzym (DE-588)4014988-2 gnd Enzymkatalyse (DE-588)4152480-9 gnd Reaktionsmechanismus (DE-588)4177123-0 gnd |
| topic_facet | Enzymkinetik Proteinfaltung Katalyse Chemische Struktur Proteine Enzym Enzymkatalyse Reaktionsmechanismus |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009231128&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT fershtalan structureandmechanisminproteinscienceaguidetoenzymecatalysisandproteinfolding |