Introduction to protein science : architecture, function, and genomics / Arthur M. Lesk, The Pennsylvania State University. -- Third edition. -- Oxford, United Kingdom : Oxford University Press, 2016. – (58.17421/L629p/3rd ed.)

Contents

Preface to the first edition

Preface to the second edition

Preface to the third edition

1 Introduction

Proteins in their biological context

The amino acids

Dogmas—central and peripheral

The relationship between amino acid sequence and protein structure is robust

Disorder in proteins

Regulation

The genetic code

With life so dependent on proteins, there is ample opportunity for things to go wrong

Genome sequences

Gene sequence determines amino acid sequence

Protein synthesis: the ribosome is the point of contact between genes and proteins--it is the fulcrum of genomics

Protein stability, denaturation, aggregation, and turnover

Description of protein structures

How do proteins develop new functions?

The study of proteins: in the laboratory, in the cell, in the computer

Spectroscopic methods of characterizing proteins in solution

Protein expression patterns in space and time: proteomics

Computing in protein science

Useful websites

Recommended reading

Exercises and Problems

2 Protein structure

Introduction

Structures of the amino acids

Protein conformation

Sidechain conformation

Stabilization of the native state

Conformational change

Protein folding patterns

Classification of protein structures

Databanks of protein structure classifications

A survey of protein structures and functions

Control of protein activity

Recommended reading

Exercises and Problems

3 Protein structure determination

Introduction

X-ray crystallography

X-ray crystallography of proteins

How accurate are the structures?

X-ray crystallography--the theoretical background

Nuclear magnetic resonance spectroscopy in structural biology

Near atomic-resolution low-temperature electron microscopy (cryo-EM)

Trajectories of conformational change

The relationship between structure determinations of isolated proteins, and protein structure and function in vivo

Protein structure prediction and modelling

Recommended reading

Exercises and Problems

4  Bioinformatics of protein sequence and structure

Introduction

Databases and information retrieval

Amino acid sequence databases

Specialized, or 'boutique', databases

Nucleic acid sequence databases

Genome databases and genome browsers

Expression and proteomics databases

Databases of macromolecular structure

Retrieval of sequences and structures

Retrieval of amino acid sequences by keyword

Retrieval of structures by keyword

Probing databanks with sequence information

Sequence alignment

Significance of alignments

Multiple sequence alignment

Analysis of structures

Superposition of structures

Databases of protein families

Classifications of protein structures

Classification and assignment of protein function

Databases of metabolic networks

Recommended reading

Exercises and Problems

5 Proteins as catalysts: enzyme structure, kinetics, and mechanism

Introduction

Reaction rates and transition states

Measurement of reaction rates

Active sites

Protein-ligand binding equilibria

Catalysis by enzymes

Enzyme kinetics

Measures of effectiveness of enzymes

Inhibitors

Multisubstrate reactions

Enzyme mechanisms

The mechanism of action of chymotrypsin

Serpins: serine proteinase inhibitors-conformational disease

Evolutionary divergence of enzymes

Motor proteins

ATP synthase

Membrane transport

Allosteric regulation of protein activity

Recommended reading

Exercises and Problems

6  Proteins with partners

Introduction

General properties of protein-protein interfaces

Multisubunit proteins

Diseases of protein aggregation

The immune system

Virus structures

Photosynthetic reaction centres

Protein-DNA interactions

Recommended reading

Exercises and Problems

7 Evolution of protein structure and function

Introduction

Protein structure classification

A case study: superpositions and alignments of pairs of proteins with increasingly more-distant relationships

Structural relationships among homologous domains

Changes in proteins during evolution give clues to the roles of residues at different positions

To what constraints are pathways of protein evolution subject?

Closed/3-barrel structures

Evolution of the globins

Phycocyanins and the globins

Evolution of NAD-binding domains of dehydrogenases

Comparison of NAD-binding domains of dehydrogenases

Structure and evolution of serine proteinases of the chymotrypsin family

Evolution of visual pigments and related molecules

How do proteins evolve new functions?

Protein evolution at the level of domain assembly

Directed evolution

Recommended reading

Exercises and Problems

8 Protein folding and design

Introduction

Why is protein folding so fast?

Thermodynamics--key concepts

Thermodynamics of protein folding

Experimental characterization of events in protein folding

The molten globule

Folding funnels

The effect of denaturants on rates of folding and unfolding: chevron plots

Relationship between native structure and folding

The hierarchical model of protein folding

How fast could a protein fold?

Protein misfolding and the GroEL-GroES chaperone protein

Protein engineering

Expanding and contracting the genetic code

Understanding the contents and layout of the common genetic code

Recommended reading

Exercises and Problems

9 Proteomics and systems biology

Introduction

Separation and analysis of proteins

Mass spectrometry

'Ome, 'ome, on the range--environmental genomics and proteomics

Microarrays

Analysis of microarray data

RNAseq

Systems biology

Networks and graphs

Dynamics, stability, and robustness

Protein complexes and aggregates

Protein interaction networks

Regulatory networks

Gene regulation

The genetic regulatory network of Saccharomyces cerevisiae

Adaptability of the yeast regulatory network

Recommended reading

Exercises and Problems

Epilogue

List of Abbreviations

Glossary

Index