Protein stucture and function

✍ Scribed by Petsko G.A.

• Publisher: New Science
• Year: 2004
• Tongue: English
• Leaves: 174
• Series: Primers in Biology
• Category: Library

✦ Synopsis

Published by New Science Press, this text introduces general principles of protein structure, folding, and function, then goes beyond these basics to tackle the conceptual basis of inferring structure and function from genomic sequence. It is the first book in a series, Primers in Biology, employing a modular design in which chapters are divided into topics, each occupying one two-page spread that includes the relevant text, illustrations (in full color), definitions, and references. The book has five chapters. The first is an introduction to the principles of protein structure and folding, with emphasis on proteins' biophysical properties. The second describes the principles of the main biochemical functions of proteins, namely binding and catalysis, with a short section on the properties of structural proteins. Chapter 3 covers the regulation of protein function, containing concise descriptions of all the regulatory mechanisms that operate on proteins, from pH to phosphorylation, with several sections on protein switches based on nucleotide hydrolysis. Chapter 4 introduces the principles whereby structure and function are deduced from sequence, with illustrative examples. The final chapter addresses how data on protein structure is gathered, interpreted, and presented. Written for upper-level undergraduates and beginning graduate students, Protein Structure and Function will also be useful for working scientists needing an up-to-date introduction to the field.

✦ Table of Contents

1: From Sequence to Structure......Page 1
1-0 Overview: Protein Function and Architecture......Page 2
1-1 Amino Acids......Page 4
1-2 Genes and Proteins......Page 6
1-3 The Peptide Bond......Page 8
1-4 Bonds that Stabilize Folded Proteins......Page 10
1-5 Importance and Determinants of Secondary Structure......Page 12
1-6 Properties of the Alpha Helix......Page 14
1-7 Properties of the Beta Sheet......Page 16
1-8 Prediction of Secondary Structure......Page 18
1-9 Folding......Page 20
1-10 Tertiary Structure......Page 22
1-11 Membrane Protein Structure......Page 24
1-12 Protein Stability: Weak Interactions and Flexibility......Page 26
1-13 Protein Stability: Post-Translational Modifications......Page 28
1-14 The Protein Domain......Page 30
1-15 The Universe of Protein Structures......Page 32
1-16 Protein Motifs......Page 34
1-17 Alpha Domains and Beta Domains......Page 36
1-18 Alpha/Beta, Alpha+Beta and Cross-Linked Domains......Page 38
1-19 Quaternary Structure: General Principles......Page 40
1-20 Quaternary Structure: Intermolecular Interfaces......Page 42
1-21 Quaternary Structure: Geometry......Page 44
1-22 Protein Flexibility......Page 46
2: From Structure to Function......Page 48
2-0 Overview: The Structural Basis of Protein Function......Page 49
2-1 Recognition, Complementarity and Active Sites......Page 51
2-2 Flexibility and Protein Function......Page 53
2-3 Location of Binding Sites......Page 55
2-4 Nature of Binding Sites......Page 57
2-5 Functional Properties of Structural Proteins......Page 59
2-6 Catalysis: Overview......Page 61
2-7 Active-Site Geometry......Page 63
2-8 Proximity and Ground-State Destabilization......Page 65
2-9 Stabilization of Transition States and Exclusion of Water......Page 67
2-10 Redox Reactions......Page 69
2-11 Addition/Elimination, Hydrolysis and Decarboxylation......Page 71
2-12 Active-Site Chemistry......Page 73
2-13 Cofactors......Page 75
2-14 Multi-Step Reactions......Page 77
2-15 Multifunctional Enzymes......Page 79
2-16 Multifunctional Enzymes with Tunnels......Page 81
3: Control of Protein Function......Page 83
3-0 Overview: Mechanisms of Regulation......Page 84
3-1 Protein Interaction Domains......Page 86
3-2 Regulation by Location......Page 88
3-3 Control by pH and Redox Environment......Page 90
3-4 Effector Ligands: Competitive Binding and Cooperativity......Page 92
3-5 Effector Ligands: Conformational Change and Allostery......Page 94
3-6 Protein Switches Based on Nucleotide Hydrolysis......Page 96
3-7 GTPase Switches: Small Signaling G Proteins......Page 98
3-8 GTPase Switches: Signal Relay by Heterotrimeric GTPases......Page 100
3-9 GTPase Switches: Protein Synthesis......Page 102
3-10 Motor Protein Switches......Page 104
3-11 Regulation by Degradation......Page 106
3-12 Control of Protein Function by Phosphorylation......Page 108
3-13 Regulation of Signaling Protein Kinases: Activation Mechanism......Page 110
3-14 Regulation of Signaling Protein Kinases: Cdk Activation......Page 112
3-15 Two-Component Signaling Systems in Bacteria......Page 114
3-16 Control by Proteolysis: Activation of Precursors......Page 116
3-17 Protein Splicing: Autoproteolysis by Inteins......Page 118
3-18 Glycosylation......Page 120
3-19 Protein Targeting by Lipid Modifications......Page 122
3-20 Methylation, N-acetylation, Sumoylation and Nitrosylation......Page 124
4: From Sequence to Function: Case Studies in Structural and Functional Genomics......Page 126
4-0 Overview: From Sequence to Function in the Age of Genomics......Page 127
4-1 Sequence Alignment and Comparison......Page 129
4-2 Protein Profiling......Page 131
4-3 Deriving Function from Sequence......Page 133
4-4 Experimental Tools for Probing Protein Function......Page 135
4-5 Divergent and Convergent Evolution......Page 137
4-6 Structure from Sequence: Homology Modeling......Page 139
4-7 Structure from Sequence: Profile-Based Threading and “Rosetta”......Page 141
4-8 Deducing Function from Structure: Protein Superfamilies......Page 143
4-9 Strategies for Identifying Binding Sites......Page 145
4-10 Strategies for Identifying Catalytic Residues......Page 147
4-11 TIM Barrels: One Structure with Diverse Functions......Page 149
4-12 PLP Enzymes: Diverse Structures with One Function......Page 151
4-13 Moonlighting: Proteins with More than One Function......Page 153
4-14 Chameleon Sequences: One Sequence with More than One Fold......Page 155
4-15 Prions, Amyloids and Serpins: Metastable Protein Folds......Page 157
4-16 Functions for Uncharacterized Genes: Galactonate Dehydratase......Page 159
4-17 Starting from Scratch: A Gene Product of Unknown Function......Page 161
5: Structure Determination......Page 163
5-1 The Interpretation of Structural Information......Page 164
5-2 Structure Determination by X-Ray Crystallography and NMR......Page 166
5-3 Quality and Representation of Crystal and NMR Structures......Page 168
Glossary......Page 170