Advances in Protein Chemistry: Evolutionary

This is the first high-quality, comprehensive overview of the field of evolutionary protein design. Topics include new protein design strategies, the structures of laboratory-evolved proteins, the evolution of non-natural enzyme functions, and the theory of laboratory evolution.

Preface

ix

New Functions from Old Scaffolds: How Nature Reengineers Enzymes for New Functions

Patricia C. Babbitt

John A. Gerlt

Introduction

1

(2)

Defining Protein Superfamilies

3

(3)

The Enolase Superfamily: A Paradigm for Understanding How Nature Evolved Enzymes for New Functions

6

(15)

Studies of Other Superfamilies and Fold Classes

21

(5)

Conclusions

26

(1)

References

26

(3)

Evolution of Protein Function by Domain Swapping

Marc Ostermeier

Stephen J. Benkovic

Introduction

29

(1)

Terminology

30

(1)

Evolution of Proteins in Nature by Domain Swapping

31

(12)

Domain Swapping for Protein Engineering

43

(16)

Methodologies

59

(8)

Perspective

67

(12)

References

68

(11)

Rational Evolutionary Design: The Theory of In Vitro Protein Evolution

Christopher A. Voigt

Stuart Kauffman

Zhen-Gang Wang

Introduction

79

(2)

Sequence Space and Fitness Landscapes

81

(16)

Modeling Directed Evolution

97

(41)

Rational Evolutionary Design

138

(14)

Summary and Conclusions

152

(9)

References

154

(7)

Temperature Adaptation of Enzymes: Lessons from Laboratory Evolution

Patrick L. Wintrode

Frances H. Arnold

Introduction

161

(3)

Influence of Temperature on Enzymes

164

(3)

Studies of Natural Extremophilic Enzymes

167

(6)

Directed Evolution

173

(35)

Stability, Flexibility, and Catalytic Activity

208

(8)

Why Are Proteins Marginally Stable?

216

(2)

Why Are Thermophilic Enzymes Poorly Active at Low Temperature?

218

(1)

Conclusions

219

(8)

References

221

(6)

Structural Analysis of Affinity Matured Antibodies and Laboratory-Evolved Enzymes

M. Cecilia Orencia

Michael A. Hanson

Raymond C. Stevens

Introduction

227

(1)

Structural Studies of Antibody Affinity Maturation

228

(16)

Structural Studies of Enzyme Directed Evolution

244

(10)

Conclusions

254

(7)

References

257

(4)

Molecular Breeding: The Natural Approach to Protein Design

Jon E. Ness

Stephen B. Del Cardayre

Jeremy Minshull

Willem P. C. Stemmer

Introduction

261

(2)

The Need for Better Proteins

263

(1)

Strategies for Optimizing Proteins

264

(13)

Screening Is Key

277

(4)

Beyond Proteins

281

(4)

Concluding Remarks

285

(8)

References

286

(7)

Analysis of Large Libraries of Protein Mutants Using Flow Cytometry

George Georgiou

Introduction

293

(1)

Library Screening Technologies

294

(7)

Cell Surface Display Technologies

301

(2)

Library Screening by Flow Cytometry

303

(8)

Concluding Remarks

311

(6)

References

311

(6)

From Catalytic Asymmetric Synthesis to the Transcriptional Regulation of Genes: In Vivo and In Vitro Evolution of Proteins

Carlos F. Barbas III

Christoph Rader

David J. Segal

Benjamin List

James M. Turner

Introduction and Scope of Review

317

(1)

Selecting and Evolving Therapeutic Human Antibodies

318

(13)

Directing Evolution at the Level of Chemical Mechanism: Aldolase Antibodies and Asymmetric Catalysis

331

(18)

Multiple Hapten Selection: Refining the Active Site of a Catalytic Antibody by In Vitro Selection

349

(1)

Selection and Evolution of Novel DNA-Binding Proteins: From Principles to Applications

350

(17)

References

363

(4)

In Vitro Selection and Evolution of Proteins

Andreas Pluckthun

Christiane Schaffitzel

Jozef Hanes

Lutz Jermutus

Introduction

367

(5)

The Key to In Vitro Protein Evolution: Cell-Free Translation

372

(2)

In Vitro Selection Strategies

374

(14)

Applications of Ribosome Display

388

(10)

Perspectives of Directed In Vitro Evolution

398

(7)

References

399

(6)

Author Index

405

(24)

Subject Index

429

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Advances in Protein Chemistry: Evolutionary Protein Design

Summary

Table of Contents

Supplemental Materials