Use of X-Ray Crystallography in the Design of Antiviral Agents

Contributors

Foreword

Preface


1. Membrane Fusion by Influenza Viruses and the Mechanism of Action of Amantadine

I. Studies on Membrane Fusion

II. The Mechanism of Action of Amantadine

III. Conclusions

References


2. Epitope Mapping and Idiotypy of the Antibody Response to Influenza Neuraminidase

I. Introduction

II. Identification of a Dominant Antigenic Site on N9 Neuraminidase

III. Anti-Idiotypes for Induction of Anti-N9 Neuraminidase Immune Responsiveness

References


3. Structure of a Human Histocompatibility Molecule: Implications for Its Interactions with Peptides and T Cell Receptors

I. Introduction

II. The Structure of HLA-A2

III. T Cell Receptor Structure

IV. Future Work and Implications for Drug Design

References


4. Structure of the Adenovirus Virion

I. Introduction

II. Virion Proteins

III. Hexon Structure

IV. Arrangement of Hexons in the Capsid

V. Position of Polypeptide IX

VI. Conclusions

References


5. Crystal Structures of Influenza Virus Neuraminidase Complexed with Monoclonal Antibody Fab Fragments

I. Introduction

II. The Influenza Virus Neuraminidase

III. Escape Mutants

IV. Structure of Escape Mutants

V. Structure of a Second N9 Neuraminidase-Fab Complex (NC 10 Fab)

VI. Mechanism of Inhibition of Neuraminidase Activity by Antibody

VII. Change in Antibody Structure

VIII. Influenza Type B Neuraminidase

IX. Sendai HN

References


6. An Approach to the Design of Anti-Influenza Agents

I. Introduction

II. Hemagglutinin Host-Cell Receptor Binding Site

III. Determination of Favorable Ligand Binding Regions in the Hemagglutinin Host-Cell Receptor Binding Site

IV. Design of Ligands to Block the Attachment of Influenza Viruses to Cells

V. Conclusions

References


7. Immunochemical and Crystallographic Studies on the Interaction between Antibody and a Synthetic Peptide of Influenza Hemagglutinin

I. Antigenic Properties of a Synthetic Peptide of Influenza Virus Hemagglutinin

II. Identification of the Amino Acid Residues Involved in Antibody Binding

III. Stoichiometry of the Interaction between Antibody and Peptide Antigen

IV. Properties of Anti-Idiotypic Antibodies Raised Against MAbs 1 /1 and 2/1

V. Conclusions

References


8. Structural Studies of Antipeptide Antibodies

I. Introduction

II. Anti-Hemagglutinin Peptide Fabs

III. Anti-Mhr Peptide Fabs

References


9. Complexes of Peptides, Nucleotides, and Fluorescein with Immunoglobulin Fragments: Effects of Solvent on Crystal Structures and Ligand Binding

I. Introduction

II. Binding Properties of the Meg Bence-Jones Dimer

III. Monoclonal Autoantibody with Activity against Single-Stranded DNA

IV. Three-Dimensional Structure of a Fluorescein-Fab Complex Crystallized in MPD

References


10. Neutralizing Rhino viruses with Antiviral Agents that Inhibit Attachment and Uncoating

I. Introduction

II. Canyon Structure

III. Alterations of the Canyon Shape that Inhibit Attachment

IV. Antiviral Agents that Interfere with Capsid Function

V. Conclusion

References


11. Structural Determinants of Serotype Specificity, Host Range, and Thermostability in Poliovirus

I. Introduction

II. Poliovirus Structure

III. Comparison of the Structures of P1/Mahoney and P3/Sabin

IV. Serotype-Specific Conformations in Antigenic Site 1

V. What Are the Determinants of Mouse Virulence?

VI. Molecular Modeling of Loop Structures in Poliovirus

VII. Newly Recognized Components of the Virion Structure

VIII. Temperature Sensitivity in the P3/Sabin Strain

References


12. Structure of Foot-and-Mouth Disease Virus

I. Introduction

II. Determination of the Three-Dimensional Structure

III. An Overview of the Structure of the Capsid

IV. Antigenic Surface of Foot-and-Mouth Disease Virus

V. Peptide Vaccines

VI. Cell Attachment Site

VII. Uncoating, Assembly, and Disassembly

VIII. Conclusions

References


13. Escape Mutant Analysis of a Drug-Binding Site can be Used to Map Functions in the Rhinovirus Capsid

I. Introduction

II. Results

III. Discussion

References


14. Quantitative Structure-Activity Relationships and Biological Consequences of Picornavirus Capsid-Binding Compounds

I. Introduction

II. Enantiomeric Effects

III. Structure-Activity Studies Based on Chain Length

IV. A Model for HRV14 Activity

V. Binding of Disoxaril

VI. Mechanism of Action

VII. Antiviral Activity in Virus-Infected Animals

VIII. Conclusions

References


15. Comparative Structures of Two Lysozyme-Antilysozyme Complexes

I. Introduction

II. HyHEL-5 and HyHEL-10 Fab Complexes with Lysozyme

References


16. Structural Basis of Antigen-Antibody Recognition

I. Introduction

II. Crystallographic Studies of Fab-Lysozyme Complexes

III. Idiotype-Anti-Idiotype Interactions

IV. Solubilization of the T Cell Antigen Receptor

References


17. Analysis of Antibody-Protein Interactions Utilizing Site-Directed Mutagenesis and a New Evolutionary Variant of Lysozyme

I. Introduction

II. Interactions of HyHEL-5 with HEL

III. Interactions of HyHEL-10 and HyHEL-8 with HEL

IV. Summation and Conclusion

References


18. Approaches toward the Design of Proteins of Enhanced Thermostability

I. Introduction

II. Hydrophobic Interactions

III. Hydrogen Bonding

IV. Helix-Dipole Interactions

V. Substitutions That Decrease the Entropy of Unfolding

VI. Removal of Strain

VII. Disulfide Bridges

VIII. Conclusions

References


19. Interplay among Enzyme Mechanism, Protein Structure, and the Design of Serine Protease Inhibitors

I. Introduction

II. Mechanism-Derived Inhibitors

III. Structure-Derived Inhibitors

References


20. Applications of Crystallographic Databases in Molecular Design

I. Introduction

II. Description of Crystallographic Databases

III. Molecular Design and Databases

IV. Examples of Database Utilization

V. Application to Design

VI. Conclusions

References


21. Virus Structure and the AIDS Problem: Strategies for Antiviral Design Based on Structure

I. Introduction

II. Overall Structure of HIV and Genomic Arrangement

III. A Detailed Look at the HIV Proteins in Light of Other Viral Structures

IV. Conclusion

References


22. Analysis of the Reverse Transcriptase of Human Immunodeficiency Virus Expressed in Escherichia Coli

Text

References


23. Structural Studies on Human Immunodeficiency Virus Reverse Transcriptase

I. Introduction

II. Production and Purification of Recombinant HIV RT

III. Crystallization of HIV RT

IV. Results

V. Conclusions

References


24. Human Immunodeficiency Virus (Type 1) Protease: Enzymology and Three-Dimensional Structure of a New AIDS Drug Target

I. Introduction

II. Biochemistry of the HIV-1 Protease

III. Crystal Structure of the HIV-1 Protease

References


25. Oligomeric Structure of Retroviral Envelope Glycoproteins

I. Introduction

II. Materials and Methods

III. Results

IV. Discussion

References


26. Tumor Necrosis Factor: A Nonviral Jelly Roll

I. Introduction

II. Structure Determination

III. Structure

IV. Conclusions

References

Index