Quantum tunnelling in enzyme-catalysed reactions / edited by Rudolf K. Allemann, Nigel S. Scrutton.

Format:

Book

Contributor:

Allemann, Rudolf K. (Rudolf Konrad)

Scrutton, Nigel S.

Rosengarten Family Fund.

Series:

RSC biomolecular sciences

Language:

English

Subjects (All):

Tunneling (Physics).

Quantum biochemistry.

Enzymes.

Catalysis.

Physical Description:

xxv, 385 pages : illustrations (some color) ; 25 cm.

Place of Publication:

Cambridge, UK : Royal Society of Chemistry, [2009]

Summary:

In recent years, there has been an explosion in knowledge and research associated with the field of enzyme catalysis and H-tunnelling. Rich in its breadth and depth, this introduction to modern theories and methods of study is suitable for experienced researchers and those new to the subject.

Edited by two leading experts, and bringing together the foremost practitioners in the field, this up-to-date account of a rapidly developing field sits at the interface between biology, chemistry and physics. It covers computational, kinetic and structural analysis of tunnelling and the synergy in combining these methods (with a major focus on H-tunnelling reactions in enzyme systems).

The book starts with a brief overview of proton and electron transfer history by Nobel Laureate, Rudolph A. Marcus. The reader is then guided through chapters covering almost every aspect of reactions in enzyme catalysis ranging from descriptions of the relevant quantum theory and quantum/classical theoretical methodology to the description of experimental results. The theoretical interpretation of these large systems includes both quantum mechanical and statistical mechanical computations, as well as more simple approximate models.

Most of the chapters focus on enzymatic catalysis of hydride, proton and H-transfer, an example of the latter being proton coupled electron transfer. There is also a chapter on electron transfer in proteins. This is timely since the theoretical framework developed fifty years ago for treating electron transfers has now been adapted to H-transfers and electron transfers in proteins.

Accessible in style, this book is suitable for a wide audience and will be particularly useful to advanced level undergraduates, postgraduates and early postdoctoral researchers.

Contents:

Chapter 1 The Transition-State Theory Description of Enzyme Catalysis for Classically Activated Reactions / Barry K. Carpenter

1.1 Introduction 1

1.2 Quantifying the Catalytic Activity of Enzymes 2

1.3 Free-Energy Analysis of Enzyme Catalysis 4

1.4 Transition-State Stabilisation or Ground-State Destabilisation? 8

1.5 Selective Stabilisation of Transition Structures by Enzymes 11

1.6 Enzyme Flexibility and Dynamics 14

References 16

Chapter 2 Introduction to Quantum Behaviour - A Primer / Sam P. de Visser

2.1 Introduction 18

2.1.1 Classical Mechanics 19

2.2 Quantum Mechanics 19

2.2.1 Heisenberg Uncertainty Principle 19

2.2.2 The Schrödinger Equation 20

2.3 Electronic-Structure Calculations 22

2.3.1 Born-Oppenheimer Approximation 22

2.3.2 Hartree-Fock Theory 22

2.3.3 Basis Sets 25

2.3.4 Zero-Point Energy 26

2.4 Density Functional Theory 28

2.4.1 DFT Calculations of Free Energies of Activation of Enzyme Models 30

2.4.2 DFT Calculations of Kinetic Isotope Effects 31

2.5 Quantum-Mechanics/Molecular-Mechanics Methods 32

2.6 Summary and Outlook 34

References 34

Chapter 3 Quantum Catalysis in Enzymes / Agnieszka Dybala-Defratyka, Piotr Paneth, Donald G. Truhlar

3.1 Introduction 36

3.2 Theory 39

3.2.1 Gas-Phase Variational Transition-State Theory 39

3.2.2 The Transmission Coefficient 42

3.2.3 Ensemble Averaging 51

3.3 Examples 55

3.3.1 Liver Alcohol Dehydrogense - A Workhorse for Studying Hydride Transfer 55

3.3.2 Dihydrofolate Reductase - A Paradigmatic System 56

3.3.3 Soybean-Lipoxygenase-1 and Methylmalonyl-CoA Mutase - Enzymes Catalysing Hydrogen Atom Transfer Reactions that Exhibit the Largest KIEs Reported for any Biological System 60

3.3.4 Other Systems and Perspectives 62

3.4 Concluding Remarks 66

Appendix - Quantum-Mechanical Rate Theory 67

Acknowledgments 67

References 67

Chapter 4 Selected Theoretical Models and Computational Methods for Enzymatic Tunnelling / Sharon Hammes-Schiffer

4.1 Introduction 79

4.2 Vibronically Nonadiabatic Reactions: Proton-Coupled Electron Transfer 80

4.2.1 Theory 81

4.2.2 Application to Lipoxygenase 85

4.3 Predominantly Adiabatic Reactions: Proton and Hydride Transfer 89

4.3.1 Theory 90

4.3.2 Application to Dihydrofolate Reductase 94

4.4 Emerging Concepts about Enzyme Catalysis 97

Acknowledgments 100

References 101

Chapter 5 Kinetic Istope Effects from Hybrid Classical and Quantum Path Integral Computations / Jiali Gao, Kin-Yiu Wong, Dan T. Major, Alessandro Cembran, Lingchun Song, Yen-lin Lin, Yao Fan, Shuhua Ma

5.1 Introduction 105

5.2 Theoretical Background 107

5.2.1 Path Integral Quantum Transition-State Theory 107

5.2.2 Centroid Path Integral Simulations 110

5.2.3 Kinetic Isotope Effects 111

5.3 Potential-Energy Surface 116

5.3.1 Combined QM/MM Potentials 116

5.3.2 The MOVB Potential 118

5.4 Computational Details 119

5.5 Illustrative Examples 120

5.5.1 Proton Transfer between Nitroethane and Acetate Ion 120

5.5.2 The Decarboxylation of N-Methyl Picolinate 123

5.5.3 Proton Transfer between Chloroacetic Acid and Substituted Α-Methoxystyrenes 126

5.6 Concluding Remarks 126

Acknowledgments 127

References 127

Chapter 6 Beyond Tunnelling Corrections: Full Tunnelling Models for Enzymatic C-H Activation Reactions / Judith P. Klinman

6.1 Introduction to Enzymatic C-H Activation Reactions 132

6.1.1 Methods of Study 132

6.1.2 The Semiclassical Origin of the Kinetic Isotope Effect 135

6.2 Detection of Hydrogen Tunnelling in the Context of a "Tunnelling Correction" 136

6.2.1 The Bell Correction 136

6.2.2 Implications for Swain-Schaad Relationships 137

6.2.3 Implication for Arrhenius Behaviour 139

6.3 Nonclassical Behaviour that Fails to Conform to the Tunnelling Correction 142

6.3.1 Swain-Schaad Relationships 142

6.3.2 Arrhenius-Behaviour Deviations 143

6.4 Full Tunnelling Behaviour under Physiological Conditions 145

6.4.1 Formalising H-transfer in the Context of Electron Tunnelling 145

6.4.2 A Simple Physical Model for H-tunnelling 145

6.5 Soybean Lipoxygenase-1 (SLO-1) as a Prototype of Full Tunnelling in an Enzyme 149

6.5.1 Overview of the Isotopic Properties of SLO-1 Catalysis 149

6.5.2 The Temperature Dependence of KIEs in the SLO-1 Reaction 150

6.6 Conclusions and Implications for Our Understanding of Enzyme Catalysis 155

References 157

Chapter 7 Quantum Effects in Enzyme Kinetics / Arundhuti Sen, Amnon Kohen

7.1 Introduction 161

7.2 Kinetic Isotope Effects: Basic Terms and Concepts 163

7.2.1 Defining KIEs 163

7.2.2 Swain-Schaad Relationships for 1° and 2° KIEs 164

7.2.3 Kinetic Complexity 165

7.2.4 Coupling and Coupled Motion 168

7.2.5 Experimental Methods and Design 168

7.3 KIEs as Probes for Tunnelling 170

7.3.1 The Size of the KIE 170

7.3.2 Comparison of 2° KIEs and 2° EIEs 171

7.3.3 Deviations from Semiclassical 2° Swain-Schaad Relationships 171

7.3.4 Temperature Dependence of the KIEs 172

7.4 Test Cases: Alcohol Dehydrogenase, Dihydrofolate Reductase and Thymidylate Synthase 174

7.4.1 Alcohol Dehydrogenase 174

7.4.2 Dihydrofolate Reductase 175

7.4.3 Thymidylate Synthase 176

7.5 Conclusions 176

References 176

Chapter 8 Direct Methods for the Analysis of Quantum-Mechanical Tunnelling: Dihydrofolate Reductase / E. Joel Loveridge, Rudolf K. Allemann

8.1 Introduction 179

8.1.1 The Kinetic Isotope Effect 180

8.1.2 The Significance of Tunnelling in Enzymatic Reactions 182

8.1.3 Experimental Methods of Observing the Chemical Step of the Reaction 184

8.2 Dihydrofolate Reductase: A Case Study 186

8.2.1 DHFR from Escherichia coli 188

8.2.2 DHFR from the Thermophile Bacillus stearothermophilus 192

8.2.3 DHFR from the Hyperthermophile Thermotoga Maritima 192

8.3 Temperature Dependence of the KIEs for other Homologous Enzymes 193

8.4 Conclusions 194

References 195

Chapter 9 Probing Coupled Motions in Enzymatic Hydrogen Tunnelling Reactions: Beyond Temperature-Dependence Studies of Kinetic Isotope Effects / Sam Hay, Michael J. Sutcliffe, Nigel S. Scrutton

9.1 Dynamics and Full Tunnelling Models for Enzymatic H-transfer 199

9.1.1 Towards a More Detailed Understanding of the Temperature Dependence of KIEs 201

9.1.2 Identifying a Promoting Motion in AADH and Rationalising the Apparent Temperature Independence of the KIE For Substrate C-H/D Bond Breakage 201

9.2 Pressure as a Probe of Hydrogen Tunnelling 203

9.2.1 Steady-State Analysis of the Pressure Dependence of H-Transfer: A Case Study with Alcohol Dehydrogenase 203

9.2.2 Pressure Variation and Direct Analysis of the Chemical Step: A Case Study with Morphinone Reductase 205

9.2.3 Modelling the Pressure Dependence of an Environmentally Coupled H-tunnelling Reaction 208

9.3 Other Probes of Tunnelling: Future Prospects for Experimental Studies 209

9.3.1 Secondary KIEs 209

9.3.2 Driving Force 211

9.3.3 Viscosity 211

9.3.4 Multiple Reactive Configurations and a Place for Single-Molecule Measurements 213

9.4 Conclusions 215

References 216

Chapter 10 Computational Simulations of Tunnelling Reactions in Enzymes / Jiayun Pang, Nigel S. Scrutton, Michael J.

Sutcliffe

10.1 Introduction 219

10.2 Molecular Mechanical Methods 220

10.3 Quantum Mechanical Methods 222

10.4 Combined Quantum Mechanical/Molecular Mechanical Methods 222

10.5 Improving Semiempirical QM Calculations 223

10.6 Calculation of Potential Energy Surfaces and Free Energy Surfaces 224

10.7 Simulation of the H-tunnelling Event 224

10.8 Calculation of H-tunnelling Rates and Kinetic Isotope Effects 225

10.9 Analysing Molecular Dynamics Trajectories 225

10.10 A Case Study: Aromatic Amine Dehydrogenase (AADH) 226

10.10.1 Preparation of the System 226

10.10.2 Analysis of the H-tunnelling Step in AADH 229

10.10.3 Analysis of the Role of Promoting Motions in Driving Tunnelling 232

10.10.4 Comparison of Short-Range Motions in AADH with Long-Range Motions in Dihydrofolate Reductase 235

10.11 Summary 238

References 238

Chapter 11 Tunnelling does not Contribute Significantly to Enzyme Catalysis, but Studying Temperature Dependence of Isotope Effects is Useful / Hanbin Liu, Arieh Warshel

11.1 Introduction 242

11.2 Methods 244

11.3 Simulating Temperature Dependence of KIEs in Enzymes 248

11.4 Concluding Remarks 256

Acknowledgement 264

References 264

Chapter 12 The Use of X-ray Crystallography to Study Enzymic H-tunnelling / David Leys

12.1 Introduction 268

12.2 X-ray Crystallography: A Brief Overview 269

12.2.1 Accuracy of X-ray Diffraction Structures 270

12.2.2 Dynamic Information from X-ray Crystallography 275

12.3 Examples of H-tunnelling Systems Studied by Crystallography 278

12.3.1 Crystallographic Studies of AADH Catalytic Mechanism 278

12.3.2 Crystallographic Studies of MR 284

12.4 Conclusions 286

References 287

Chapter 13 The Strengths and Weaknesses of Model Reactions for the Assessment of Tunnelling in Enzymic Reactions / Richard L. Schowen

13.1 Model Reactions for Biochemical Processes 292

13.2 Model Reactions Relevant to Enzymic Tunnelling 294

13.3 Isotope Effect Temperature Dependences and the Configurational-Search Framework (CSF) for their Interpretation 294

13.3.1 The Traditionally Dependent Category 296

13.3.2 The Underdependent Tunnelling Category 296

13.3.3 The Overdependent Tunnelling Category 297

13.4 Example 1. Hydride Transfer in a Thermophilic Alcohol Dehydrogenase 298

13.4.1 The Kirby-Walwyn Intramolecular Model Reaction 298

13.4.2 The Powell-Bruice Tunnelling Model Reaction 300

13.4.3 Enzymic Tunnelling in Alcohol Dehydrogenases 301

13.4.4 Model Reactions and the Catalytic Power of Alcohol Dehydrogenase 303

13.5 Example 2. Hydrogen-Atom Transfer in Methylmalonyl Coenzyme A Mutase (MCM) 304

13.5.1 Nonenzymic Tunnelling in the Finke Model Reactions for MCM 305

13.5.2 Enzymic Tunnelling in MCM 308

13.5.3 Model Reactions and MCM Catalytic Power 309

13.6 The Roles of Theory in the Comparison of Model and Enzymic Reactions 310

13.7 Model Reactions, Enzymic Accelerations, and Quantum Tunnelling 310

References 311

Chapter 14 Long-Distance Electron Tunnelling in Proteins / Alexei A. Stuchebrukhov

14.1 Introduction 314

14.2 Electronic Coupling and Tunnelling Pathways 315

14.2.1 Direct Method 317

14.2.2 Avoided Crossing 317

14.2.3 Application of Koopmans' Theorem 318

14.2.4 Generalised Mulliken-Hush Method 319

14.2.5 The Propagator Method 320

14.2.6 Protein Pruning 322

14.2.7 Tunnelling Pathways 323

14.3 The Method of Tunnelling Currents 324

14.3.1 General Relations 324

14.3.2 Many-Electron Picture 328

14.4 Many-Electron Aspects 331

14.4.1 One Tunnelling Orbital (OTO) Approximation and Polarisation Effects 333

14.4.2 The Limitation of the SCF Description of Many-Electron Tunnelling 334

14.4.3 Correlation Effects. Polarisation Cloud Dynamics. Beyond Hartree-Fock Methods 335

14.4.4 Quantum Interference Effects. Quantised Vertices 336

14.4.5 Electron Transfer or Hole Transfer? Exchange Effects 338

14.5 Dynamical Aspects 339

Acknowledgments 341

References 342

Chapter 15 Proton-Coupled Electron Transfer: The Engine that Drives Radical Transport and Catalysis in Biology / Steven Y. Reece, Daniel G. Nocera

15.1 Introduction 345

15.2 PCET Model Systems 351

15.2.1 Unidirectional PCET Networks 351

15.2.2 Bidirectional PCET Networks 357

15.2.3 PCET Biocatalysis 357

15.3 PCET in Enzymes: A Study of Ribonucleotide Reductase 360

15.3.1 The PCET Pathway in RNR 361

15.3.2 PCET in the Β2 Subunit of RNR 361

15.3.3 PCET in α2 Subunit of RNR: PhotoRNRs 364

15.3.4 A Model for PCET in RNR 368

15.4 Concluding Remarks 370

Acknowledgements 370

References 370.

Notes:

Includes bibliographical references and index.

Local Notes:

Acquired for the Penn Libraries with assistance from the Rosengarten Family Fund.

ISBN:

9780854041220

0854041222

OCLC:

276224533

Publisher Number:

99934943063