Petsko G., Ringe D. Protein Stucture and Function

New Science Press, 2004. - 184 p.The genomics revolution is providing gene sequences in exponentially increasing numbers. Converting this sequence information into functional information for the gene products coded by these sequences is the challenge for post-genomic biology. The first step in this process will often be the interpretation of a protein sequence in terms of the threedimensional structure into which it folds. This chapter summarizes the basic concepts that underlie the relationship between sequence and structure and provides an overview of the architecture of proteins.From Sequence to Structure
Overview: Protein Function and Architecture
Amino Acids
Genes and Proteins
The Peptide Bond
Bonds that Stabilize 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: Weak Interactions and Flexibility
Protein Stability: Post-Translational Modifications
The Protein Domain
The Universe of Protein Structures
Protein Motifs
From Sequence to Function:
Alpha Domains and Beta Domains
Alpha/Beta, A lpha+Beta and Cross-Linked Domains
Quaternary Structure: General Principles
Quaternary Structure: Intermodular Interfaces
Quaternary Structure: Geometry
Protein Flexibility
From Structure to Function
Overview: The Structural Basis of Protein Function
Recognition, Complementarity and Active Sites
Flexibility and Protein Function
Location of Binding Sites
Nalure 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 Reactions
Addition/Elimination, Hydrolysis and Decarboxylation
Active-Site Chemistry
Cofactors
Multi-Step Reactions
Multifunctional Enzymes
Multifunctional Enzymes with Tunnels
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 Cooperativtty
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
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 Modifications
Methylation, N-acetylation, Sumoyletion and Nitrosylation
From Sequence to Function: Case Studies in Structural and Functional Genomics
Overview: From Sequence to Function in the Age
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
Prions. Amyloids and Serpins: Metastable Protein Folds
Functions for Uncharacterized Genes: Galactonate
Starting From Scratch: A Gene Product of Unknown Function
Structure Determination
The Interpretation of Structural Information
Structure Determination by X-Ray Crystallography and NMR
Quality and Representation of Crystal and NMR Structures