1. From Sequence to Structure:.
Overview: Protein Function and Architecture.
Amino Acids.
Genes and Proteins.
The Peptide Bond.
Bonds that Stablize Folded Proteins.
Importance and Determinants of Secondary Structure.
Properties of the Alpha Helix.
Properties of the Beta Sheet.
Prediction of Secondary Structure.
Folding.
Tertiary Structure.
Membrane Protein Structure.
Protein Stability 1: Weak Interactions and Flexibility.
Protein Stability 2: Post-Translational Modifications.
The Protein Domain.
The Universe of Protein Structures.
Protein Motifs.
Alpha Domains and Beta Domains.
Alpha/Beta, Alpha+Beta and Cross-Linked Domains.
Quaternary Structure: General Principles.
Quaternary Structure: Intermolecular Interfaces.
Quaternary Structure: Geometry.
Protein Flexibility.
2. From Structure to Function:.
Overview: The Structural Basis of Protein Function.
Recognition, Complementarity and Active Sites.
Flexibility and Protein Function.
Location of Binding Sites.
Nature of Binding Sites.
Functional Properties of Structural Proteins.
Catalysis: Overview.
Active-site Geometry.
Proximity and Ground-State Destabilization.
Stabilization of Transition States and Exclusion of Water.
Redox Reaction.
Addition/Elimination, Hydrolysis and Decarboxylation.
Active-Site Chemistry.
Cofactors.
Multi-Step Reactions.
Multifunctional Enzymes.
Multifunctional Enzymes with Tunnels.
3. Control of Protein Function:.
Overview: Mechanisms of Regulation.
Protein Interaction Domains.
Regulation by Location.
Control by pH and Redox Environment.
Effector Ligands: Competitive Binding and Cooperativity.
Effector Ligands: Conformational Change and Allostery.
Protein Switches Based on Nucleotide Hydrolysis.
GTPase Switches: Small Signaling G proteins.
GTPase Switches: Signal Relay by Heterotrimeric GTPases.
Gtpase Switches: Protein Synthesis.
Motor Protein Switches.
Regulation by Degradation.
Control of Protein Function by Phosphorylation.
Regulation of Signaling Protein Kinases: Activation Mechnism.
Regulation of Signaling Protein Kinases: Cdk Activation.
Two-Component Signaling Systems in Bacteria.
Control by Proteolysis: Activation of Precursors.
Protein Splicing: Autoproteolysis by Inteins.
Glycosylation.
Protein Targeting by Lipid Modification.
Methylation, N-acetylation, Sumoylation and Nitrosylation.
4. From Sequence to Function:.
Overview: From Sequence to Function in the Age of Genomics.
Sequence Alignment and Comparison.
Protein Profiling.
Deriving Function from Sequence.
Experimental Tools for Probing Protein Function.
Divergent and Convergent Evolution.
Structure from Sequence: Homology Modeling.
Structure from Sequence: Profile-Based Threading and “Rosetta”.
Deducing Function from Structure: Protein Superfamilies.
Strategies for Identifying Binding Sites.
Strategies for Identifying Catalytic Residues.
TIM Barrels: One Structure with Diverse Functions.
PLP Enzymes: Diverse Structures with One Function.
Moonlighting: Proteins with More Than One Function.
Chameleon Sequences: One Sequence with More than One Fold.
Prions, Amyloids and Serpins: Metastable Protein Folds.
Functions for Uncharacterized Genes: Galactonate Dehydratase.
Starting from Scratch: A Gene Product of Unknown Function.
5. Structure Determination:.
The Interpretation of Structural Information.
Structure Determination by X-Ray Crystallography and NWR.
Quality and Representation of Crystal and NMR Structures
Gregory Petsko is currently the Director of the prestigious Rosensteil Center at Brandeis University. His research interests include the use of yeast genetics to study the unfolding of protein response pathway and the mechanism of action of the ABC transporter proteings.
Dagmar Ringe is currently Professor of Biochemistry and Chemistry at Brandeis University studying structure-function relationships in enzymes of particular industrial and pharmaceutical importance.
"…a valuable addition to the subject. It combines much important
basic material in one volume, but also offers a contemporary angle
through its discussion of structural and functional genomics." Mark
Parsons, University of Leeds
"I particularly like how many topics are introduced in a two page
piece, with the significant publications referenced on the same
page." Brian Bahnson, University of Delaware
"...an excellent teaching resoure for undergraduates ... covers a
broad range of topics in this expanding field...This book
definitely achieves its goal of being easy to learn from. All the
elements are there..." Catherine Brean, University College London,
IJBCB, January 2004
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