From Sequence to Structure | |
Overview: Protein Function and Architecture | p. 2 |
Amino Acids | p. 4 |
Genes and Proteins | p. 6 |
The Peptide Bond | p. 8 |
Bonds that Stabilize Folded Proteins | p. 10 |
Importance and Determinants of Secondary Structure | p. 12 |
Properties of the Alpha Helix | p. 14 |
Properties of the Beta Sheet | p. 16 |
Prediction of Secondary Structure | p. 18 |
Folding | p. 20 |
Tertiary Structure | p. 22 |
Membrane Protein Structure | p. 24 |
Protein Stability: Weak Interactions and Flexibility | p. 26 |
Protein Stability: Post-Translational Modifications | p. 28 |
The Protein Domain | p. 30 |
The Universe of Protein Structures | p. 32 |
Protein Motifs | p. 34 |
Alpha Domains and Beta Domains | p. 36 |
Alpha/Beta, Alpha+Beta and Cross-Linked Domains | p. 38 |
Quaternary Structure: General Principles | p. 40 |
Quaternary Structure: Intermolecular Interfaces | p. 42 |
Quaternary Structure: Geometry | p. 44 |
Protein Flexibility | p. 46 |
From Structure to Function | |
Overview: The Structural Basis of Protein Function | p. 50 |
Recognition, Complementarity and Active Sites | p. 52 |
Flexibility and Protein Function | p. 54 |
Location of Binding Sites | p. 56 |
Nature of Binding Sites | p. 58 |
Functional Properties of Structural Proteins | p. 60 |
Catalysis: Overview | p. 62 |
Active-Site Geometry | p. 64 |
Proximity and Ground-State Destabilization | p. 66 |
Stabilization of Transition States and Exclusion of Water | p. 68 |
Redox Reactions | p. 70 |
Addition/Elimination, Hydrolysis and Decarboxylation | p. 72 |
Active-Site Chemistry | p. 74 |
Cofactors | p. 76 |
Multi-Step Reactions | p. 78 |
Multifunctional Enzymes | p. 80 |
Multifunctional Enzymes with Tunnels | p. 82 |
Control of Protein Function | |
Overview: Mechanisms of Regulation | p. 86 |
Protein Interaction Domains | p. 88 |
Regulation by Location | p. 90 |
Control by pH and Redox Environment | p. 92 |
Effector Ligands: Competitive Binding and Cooperativity | p. 94 |
Effector Ligands: Conformational Change and Allostery | p. 96 |
Protein Switches Based on Nucleotide Hydrolysis | p. 98 |
GTPase Switches: Small Signaling G proteins | p. 100 |
GTPase Switches: Signal Relay by Heterotrimeric GTPases | p. 102 |
GTPase Switches: Protein Synthesis | p. 104 |
Motor Protein Switches | p. 106 |
Regulation by Degradation | p. 108 |
Control of Protein Function by Phosphorylation | p. 110 |
Regulation of Signaling Protein Kinases: Activation Mechanism | p. 112 |
Regulation of Signaling Protein Kinases: Cdk Activation | p. 114 |
Two-Component Signaling Systems in Bacteria | p. 116 |
Control by Proteolysis: Activation of Precursors | p. 118 |
Protein Splicing: Autoproteolysis by Inteins | p. 120 |
Glycosylation | p. 122 |
Protein Targeting by Lipid Modifications | p. 124 |
Methylation, N-acetylation, Sumoylation and Nitrosylation | p. 126 |
From Sequence to Function: Case Studies in Structural and Functional Genomics | |
Overview: From Sequence to Function in the Age of Genomics | p. 130 |
Sequence Alignment and Comparison | p. 132 |
Protein Profiling | p. 134 |
Deriving Function from Sequence | p. 136 |
Experimental Tools for Probing Protein Function | p. 138 |
Divergent and Convergent Evolution | p. 140 |
Structure from Sequence: Homology Modeling | p. 142 |
Structure From Sequence: Profile-Based Threading and "Rosetta" | p. 144 |
Deducing Function from Structure: Protein Superfamilies | p. 146 |
Strategies for Identifying Binding Sites | p. 148 |
Strategies for Identifying Catalytic Residues | p. 150 |
TIM Barrels: One Structure with Diverse Functions | p. 152 |
PLP Enzymes: Diverse Structures with One Function | p. 154 |
Moonlighting: Proteins With More Than One Function | p. 156 |
Chameleon Sequences: One Sequence with More than One Fold | p. 158 |
Prions, Amyloids and Serpins: Metastable Protein Folds | p. 160 |
Functions for Uncharacterized Genes: Galactonate Dehydratase | p. 162 |
Starting From Scratch: A Gene Product of Unknown Function | p. 164 |
Structure Determination | |
The Interpretation of Structural Information | p. 168 |
Structure Determination by X-Ray Crystallography and NMR | p. 170 |
Quality and Representation of Crystal and NMR Structures | p. 172 |
Glossary | p. 175 |
References | p. 181 |
Index | p. 189 |
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