Protein Design and the Development of New Therapeutics and Vaccines

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53,49 

New Horizons in Therapeutics

ISBN: 1468457411
ISBN 13: 9781468457414
Herausgeber: Jerry B Hook/George Poste
Verlag: Springer Verlag GmbH
Umfang: xxii, 512 S., 77 s/w Illustr., 512 p. 77 illus.
Erscheinungsdatum: 13.03.2012
Auflage: 1/1990
Produktform: Kartoniert
Einband: KT

InhaltsangabeI. Advances in the Structural Analysis of Proteins.- 1 Dynamic Processes in Proteins by X-Ray Diffraction.- 1. Dynamic Processes in Proteins.- 2. Enzyme Substrate Complexes by X-Ray Diffraction.- 3. Laue Diffraction.- 4. Reaction Synchronization.- References.- 2 Mass Spectrometric Methods for Determination of the Structure of Peptides and Proteins.- 1. Introduction.- 2. High-Mass Mass Spectrometry.- 3. Tandem Mass Spectrometry.- 3.1. Sequencing of Proteins.- 3.2. Increasing Sensitivity by Using an Array Detector.- 3.3. Computer-Aided Interpretation of CID Spectra of Peptides.- 4. Conclusion.- References.- II. Protein Folding and Stability.- 3 Protein Folding and Stability.- 1. Goals.- 2. Folding of Fragments.- 3. Trapping Folding Intermediates.- References.- 4 Genetic Analysis of Polypeptide Chain Folding and Misfolding in Vivo.- 1. Introduction.- 2. The Protein Folding Grammar.- 3. Intracellular Intermediates in Chain Folding and Assembly.- 4. Temperature-Sensitive Folding Mutations.- 5. Nonsense Mutations.- 6. Intracellular Aggregation and Inclusion Body Formation.- 7. Kinetics of Aggregate Formation.- 8. Isolation of Second-Site Suppressors of Folding Mutants.- 9. The Suppressing Amino Acid Substitutions Act at the Level of Polypeptide Chain Maturation.- 10. The Suppressors Act in the Folding of the Single Chain, Not during Chain-Chain Association.- 11. The Suppressors Increase the Efficiency of Folding of the Wild-Type Chain.- References.- 5 Unfolding and Inactivation: Genetic and Chemical Approaches to the Stabilization of T4 Lysozyme and Human Interferon Gamma against Irreversible Thermal Denaturation.- 1. Introduction.- 2. T4 Lysozyme.- 2.1. Sulfhydryl Oxidation.- 2.2. Thiol/Disulfide Interchange.- 2.3. Adsorption.- 2.4. Aggregation.- 2.5. Chemical Inactivation.- 2.6. Conclusions from T4 Lysozyme Experiments.- 3. Interferon-?.- 3.1. In Vitro Experiments.- 3.2. Genetic Experiments.- 4. General Conclusions.- 4.1. Modes of Thermal-Irreversible Denaturation.- 4.2. Strategies for Stabilizing Proteins.- References.- III. Principles of Receptor Design and Regulation.- 6 Protein-Tyrosine Kinases and Their Substrates: Old Friends and New Faces.- 1. Introduction.- 2. Isolation of Novel Protein-Tyrosine Kinases.- 3. Regulation of Protein-Tyrosine Kinase Activity: Phosphorylation of pp60c-src.- 4. Protein-Tyrosine Kinase Substrates.- References.- IV. The Guanine Nucleotide Binding Protein Family.- 7 G Proteins: A Family of Signal-Transducing Molecules.- 1. The Family of G Proteins.- 2. Distribution of G Protein ? Subunits.- 3. Regulation of ?o Levels.- 4. G Proteins as Bifurcating Signals.- 5. Organizing Principles.- References.- 8 Model of Signal Transduction by G Proteins: Roles of a Subunits and ?? Dimers in Regulation of Ionic Channels and Adenylyl Cyclase.- 1. Introduction.- 2. Mechanisms of Receptor-Mediated Activation of G Proteins.- 3. Which G-Protein Subunit Mediates the Effect of Receptors?.- 3.1. Regulation of Ionic Channels: ? or ??, and What Does Each Do to Regulation of Channel Activity?.- 3.2. Inhibitory Regulation of Adenylyl Cyclase: ?i or ???.- 3.3. What Is the Role of ?? Dimers?.- References.- 9 Structural Homologies in G-Binding Proteins.- 1. Introduction.- 2. Structural Homology in Three Dimensions.- 2.1. Elongation Factor Tu (EF-Tu).- 2.2. ras Protein p21.- 3. Sequence Homology.- 3.1. Overall Homology.- 3.2. Consensus Sequences.- 4. Homology and Functional Similarity.- References.- V. Modeling and Structure Prediction in Macromolecules.- 10 Knowledge-Based Protein Modeling and the Design of Novel Molecules.- 1. Introduction.- 2. Learning by Comparison of Structures.- 2.1. Superposition of Structures.- 2.2. Comparison of Properties and Relations.- 2.3. Clustering and Tree Construction.- 3. Rules for Tertiary Templates and Key Residues, and Their Comparison with a Sequence of an Unknown.- 3.1 Consensus Sequences for Framework Regions.- 3.2. Key Residues from Comparisons of Properties and Relations.- 3.3. Charact

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Beschreibung

InhaltsangabeI. Advances in the Structural Analysis of Proteins.- 1 Dynamic Processes in Proteins by X-Ray Diffraction.- 1. Dynamic Processes in Proteins.- 2. Enzyme Substrate Complexes by X-Ray Diffraction.- 3. Laue Diffraction.- 4. Reaction Synchronization.- References.- 2 Mass Spectrometric Methods for Determination of the Structure of Peptides and Proteins.- 1. Introduction.- 2. High-Mass Mass Spectrometry.- 3. Tandem Mass Spectrometry.- 3.1. Sequencing of Proteins.- 3.2. Increasing Sensitivity by Using an Array Detector.- 3.3. Computer-Aided Interpretation of CID Spectra of Peptides.- 4. Conclusion.- References.- II. Protein Folding and Stability.- 3 Protein Folding and Stability.- 1. Goals.- 2. Folding of Fragments.- 3. Trapping Folding Intermediates.- References.- 4 Genetic Analysis of Polypeptide Chain Folding and Misfolding in Vivo.- 1. Introduction.- 2. The Protein Folding Grammar.- 3. Intracellular Intermediates in Chain Folding and Assembly.- 4. Temperature-Sensitive Folding Mutations.- 5. Nonsense Mutations.- 6. Intracellular Aggregation and Inclusion Body Formation.- 7. Kinetics of Aggregate Formation.- 8. Isolation of Second-Site Suppressors of Folding Mutants.- 9. The Suppressing Amino Acid Substitutions Act at the Level of Polypeptide Chain Maturation.- 10. The Suppressors Act in the Folding of the Single Chain, Not during Chain-Chain Association.- 11. The Suppressors Increase the Efficiency of Folding of the Wild-Type Chain.- References.- 5 Unfolding and Inactivation: Genetic and Chemical Approaches to the Stabilization of T4 Lysozyme and Human Interferon Gamma against Irreversible Thermal Denaturation.- 1. Introduction.- 2. T4 Lysozyme.- 2.1. Sulfhydryl Oxidation.- 2.2. Thiol/Disulfide Interchange.- 2.3. Adsorption.- 2.4. Aggregation.- 2.5. Chemical Inactivation.- 2.6. Conclusions from T4 Lysozyme Experiments.- 3. Interferon-?.- 3.1. In Vitro Experiments.- 3.2. Genetic Experiments.- 4. General Conclusions.- 4.1. Modes of Thermal-Irreversible Denaturation.- 4.2. Strategies for Stabilizing Proteins.- References.- III. Principles of Receptor Design and Regulation.- 6 Protein-Tyrosine Kinases and Their Substrates: Old Friends and New Faces.- 1. Introduction.- 2. Isolation of Novel Protein-Tyrosine Kinases.- 3. Regulation of Protein-Tyrosine Kinase Activity: Phosphorylation of pp60c-src.- 4. Protein-Tyrosine Kinase Substrates.- References.- IV. The Guanine Nucleotide Binding Protein Family.- 7 G Proteins: A Family of Signal-Transducing Molecules.- 1. The Family of G Proteins.- 2. Distribution of G Protein ? Subunits.- 3. Regulation of ?o Levels.- 4. G Proteins as Bifurcating Signals.- 5. Organizing Principles.- References.- 8 Model of Signal Transduction by G Proteins: Roles of a Subunits and ?? Dimers in Regulation of Ionic Channels and Adenylyl Cyclase.- 1. Introduction.- 2. Mechanisms of Receptor-Mediated Activation of G Proteins.- 3. Which G-Protein Subunit Mediates the Effect of Receptors?.- 3.1. Regulation of Ionic Channels: ? or ??, and What Does Each Do to Regulation of Channel Activity?.- 3.2. Inhibitory Regulation of Adenylyl Cyclase: ?i or ???.- 3.3. What Is the Role of ?? Dimers?.- References.- 9 Structural Homologies in G-Binding Proteins.- 1. Introduction.- 2. Structural Homology in Three Dimensions.- 2.1. Elongation Factor Tu (EF-Tu).- 2.2. ras Protein p21.- 3. Sequence Homology.- 3.1. Overall Homology.- 3.2. Consensus Sequences.- 4. Homology and Functional Similarity.- References.- V. Modeling and Structure Prediction in Macromolecules.- 10 Knowledge-Based Protein Modeling and the Design of Novel Molecules.- 1. Introduction.- 2. Learning by Comparison of Structures.- 2.1. Superposition of Structures.- 2.2. Comparison of Properties and Relations.- 2.3. Clustering and Tree Construction.- 3. Rules for Tertiary Templates and Key Residues, and Their Comparison with a Sequence of an Unknown.- 3.1 Consensus Sequences for Framework Regions.- 3.2. Key Residues from Comparisons of Properties and Relations.- 3.3. Charact

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