Protein structure and function

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