New Chemistry And New Opportunities From The Expanding Protein Universe - Proceedings Of The 23rd International Solvay Conference On Chemistry

by Donald Hilvert, Ian A Wilson, Dennis Wolan, Kurt Wuthrich, Anne De Wit

Overview

A select group of 40 eminent scientists from all parts of the world met to consider the current state of chemical and biological knowledge on the ever-expanding protein universe, and to discuss emerging opportunities for the foreseeable future. Scientific approaches to discover, characterize, and regulate protein functions were discussed over a range of disciplines, including natural product chemistry, microbiology, enzymology, biochemistry, structural biology, chemical biology, and glycobiology. Some notable highlights included discovery of new enzymatic pathways, innovative carbohydrate chemistry, design of proteins containing unnatural amino acids, structural elucidation of complex supramolecular machines, and design and application of small molecule drugs, biologics and biosimilars.This fascinating compendium of scientific presentations and in-depth discussions affords a unique perspective on today's protein chemistry and biology as well as on the challenges for tomorrow.

Product Details

ISBN-13:	9789814616560
Publisher:	World Scientific Publishing Company, Incorporated
Publication date:	12/30/2014
Pages:	380
Product dimensions:	6.50(w) x 9.60(h) x 0.70(d)

Table of Contents

I The International Solvay Institutes xi

II Solvay Scientific Committee for Chemistry xiii

III Acknowledgements xv

IV Participants xvi

V Auditors xviii

VI Opening Address Professor M. Henncaux xix

VII Preface Professor K. Wüthrich xxi

Session 1 New Chemistry in the Expanding Protein Universe 1

1.1 Novel Chemistry Still to be Found in Nature C. T. Walsh 3

1.2 Natural Product Biosynthesis in the Genomic Age W. A. van der Dank 6

1.3 Peptide Dendrimers and Poly cyclic Peptides J.-L. Reymond 11

1.4 What can Comparative Genomics Reveal about the Mechanisms of Protein Function Evolution? N. L. Dawson R. Studer N. Furnham D. Lees S. Das J. Thornton G. Orenyo 16

1.5 Exploring Chromatin Biology Using Protein Chemistry T. W. Muir 20

1.6 Our Expanding Protein Universe A. Godzik 23

1.7 The Scientific Impact of Freely Available Chemical Probes A. M. Edwards 28

1.8 Discussions of Session 1 31

Session 2 Exploring Enzyme Families and Enzyme Catalysis 57

2.1 Mechanistic Enzymology and Catalyst Design D. Hilvert 59

2.2 Looking in New Directions for the Origins of Enzymatic Rate Accelerations J. P. Klinman 64

2.3 Computational Enzyme Design and Methods to Predict the Role of Remote Mutations K. N. Houk 70

2.4 Discovering Novel Enzymes, Metabolites and Pathways J. A. Gerlt 75

2.5 Programming New Chemistry into the Genetic Code of Cells and Animals J. W. Chin 79

2.6 Expanding the Enzyme Universe through a Marriage of Chemistry and Evolution F. H. Arnold 84

2.7 Controlled R.adical Reactions in Biology and the Importance of Metallo - Cofactor Biosynthesis J. Stubbe 90

2.8 Discussions of Session 2 94

Session 3 Microbiomes and Carbohydrate Chemistry 117

3.1 Structural Basis for Host/Commensal-Microbe Interactions in the Human Distal Gut Microbiome I. A. Wilson 119

3.2 Carbohydrate Chemistry and Biology C.-H. Wong 125

3.3 Chemical Biological Proteomics of Bacterial Protein Functionalities in the Human Distal Gut Microbiome D. W. Wolan 130

3.4 Automated Oligosaccharide Synthesis: From Insights into Fundamental Glycobiology to Vaccines and Diagnostics P. H. Seeberger

3.5 Carbohydrate-Active Enzymes in Microbiomes B. Henrissat 141

3.6 The Microbiomc(s): Microbiota, Families, Functions A. Godzik 146

3.7 N-Linked Protein Glycosylation M. Aehi 150

3.8 Discussions of Session 3 154

Session 4 GPCRs and Transporters: Ligands, Cofactors, Drug Development 177

4.1 GPCRs and Transporters: Ligands, Cofactors, Drug Development G. von Heijne 179

4.2 Studies of GPCR Conformations in Non-Crystalline Milieus K. Wüthrich 182

4.3 The Seven Transmembrane Superfamily R. C. Stevens 186

4.4 Nanobodies for the Structural and Functional Investigation of GPCR Transmembrane Signaling E. Pardon J. Steyaert 192

4.5 The Hidden Pharmacology of the Human GPCR-ome B. L. Roth 195

4.6 Structures and Reaction Mechanisms of ABC Transporters K. Locher 199

4.7 Discussions of Session 4 203

Session 5 Biologicals and Biosimilars 229

5.1 Biologicals and Biosimilars S. Ghose M. G. Grütter 231

5.2 Platform Technologies for the Artificial Pseudo-Natural Product Discovery H. Suga 237

5.3 Anticalins® & Pasylation®: New Concepts for Biopharmaceutical Drug Development from Protein Design A. Skerra 243

5.4 From Natural Antibodies to Synthetic Proteins S. S. Sidhu 249

5.5 From Intact Antibodies to Armed Antibodies D. Neri 254

5.6 Regulating Cellular Life Death and Development Using Intracellular Combinatorial Antibody Libraries R. Lerner J. Xie H. Zhang K. Yea J. Blanchard K. Baldwin 257

5.7 Nanobodies: A Universe of Variable Domains and a Toolbox for Many Trades L. Wyns 260

5.8 Discussions of Session 5 266

Session 6 Proteins in Supramolecular Machines 285

6.1 Assembly of Filamentous Type 1 Pili from Uropathogenic Escherichia Coli Strains R. Glockshuber 287

6.2 HIV Envelope and Influenza Hemagglutinin Fusion Glycoproteins and the Quest for a Universal Vaccine I. A. Wilson 293

6.3 Deconstruction of Iterative Polyketide Synthases C. A. Townsend 299

6.4 Regulating Ribosome Pausing During Translation M. V. Rodnina 305

6.5 The Molecular Mechanics of the Ribosome J. Zhou L. Lancaster Z. Guo J. P. Donahue H. F. Noller 308

6.6 Exploring the Dynamics of Supramolecular Machines with Cryo-Electron Microscopy J. Frank 313

6.7 Crystallographic Studies of Eukaryotic Ribosomes and Functional Insights N. Ban 318

6.8 Discussions of Session 6 323

Index 345