Advances in Research and Applications
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Table of contents
- Cover
- Contentsvii
- Prefacexiii
- Chapter 1. Protein Folding and Deficiencies Caused by Dominant-Negative Mutants of Hormones1
- I. Introduction2
- II. Functions of the Endoplasmic Reticulum Related to Protein Folding2
- III. Aspects of the Neuroendocrine Secretory Pathway11
- IV. Isolated Dominant-Negative Hormone Deficiency: Problems in the Secretory Pathway13
- V. Conclusions20
- References21
- Chapter 2. Structural Aspects of the G-Protein Receptor, Rhodopsin27
- I. Introduction27
- II. Seven Transmembrane Helical Hydrophobic Core of Rhodopsin32
- III. Structure of the Retinal and Its Binding Site in Rhodopsin35
- IV. Structure of Extramembranous Domains of Rhodopsin36
- V. Cytoplasmic Face of Rhodopsin39
- VI. Intradiskal Face of Rhodopsin46
- VII. Future Directions46
- References47
- Chapter 3. Molecular Modeling of Mammalian Cytochromes P450: Application to Study Enzyme Function53
- I. Introduction54
- II. Molecular Modeling Methods56
- III. Homology Models in Studies of P450 Function63
- IV. Perspectives and Conclusions80
- References83
- Chapter 4. Prostaglandin D Synthase: Structure and Function89
- I. Introduction90
- II. Pharmacologic Actions of Prostaglandin D2 and Its Metabolites90
- III. Lipocalin-Type Prostaglandin D Synthase ( β-Trace)93
- IV. Hematopoietic Prostaglandin D Synthase105
- V. Future Studies108
- References109
- Chapter 5. Steroid Dehydrogenase Structures, Mechanism of Action, and Disease121
- I. Introduction122
- II. 3α,20β -Hydroxysteroid Dehydrogenase125
- III. Aldosterone, Cortisol, Licorice, and Hypertension128
- IV. 17β -Hydroxysteroid Dehydrogenase, Inhibitors, and Cancer131
- V. Protein Sequence and Three-Dimensional Conformation139
- VI. Conclusions142
- References144
- Chapter 6. Structure-Based Inhibitor Design149
- I. Introduction150
- II. Target Selection, Cloning, and Determination of 3-D Structures152
- III. Crystallographic Water Molecules155
- IV. Computational Approaches to Lead Compound Discovery156
- V. Estimating the Theoretical Limits for Reversible Inhibitor Binding160
- VI. Connectivity, Flexibility, and Conformational Entropy162
- VII. Using Enzyme Structures in Dealing with Resistance Mutations164
- VIII. Conclusions165
- References166
- Chapter 7. Protein Folding Using Contact Maps171
- I. Introduction172
- II. Structure Representation172
- III. The Reconstruction Procedure175
- IV. Dynamics in Contact Map Space183
- V. Approximation for Free Energy189
- VI. Results195
- VII. Conclusions208
- References209
- Chapter 8. HIV Protease: Enzyme Function and Drug Resistance213
- I. Introduction214
- II. HIV PR Is a Member of the Aspartic Proteinase Family216
- III. HIV PR Structure216
- IV. Mechanism of the Substrate Cleavage and Protonation State of the Catalytic Aspartates218
- V. Substrate Specificity221
- VI. Assay Methods222
- VII. pH Optima224
- VIII. Dimer Stability226
- IX. Thermodynamic Characteristics of Inhibitor Binding228
- X. Inhibitors of HIV PR228
- XI. Introduction to Resistance to HIV PR Inhibitors230
- XII. Active Site Mutations231
- XIII. Nonactive Site Mutations233
- XIV. Cleavage Site Mutants235
- XV. Reduced Dimer Stability236
- XVI. Structural Basis of Drug Resistance237
- XVII. Biochemical Basis of Viral Fitness239
- XVIII. Cross-Resistance to Protease Inhibitors243
- XIX. Conclusions244
- References245
- Chapter 9. Ultrastructure of Cells Undergoing Apoptosis257
- I. Overview of Apoptosis257
- II. Ultrastructural Features of Cells Undergoing Apoptosis258
- III. Correlation between Ultrastructural and Biochemical Features of the Cells Undergoing Apoptosis261
- IV. Conclusion265
- References265
- Chapter 10. Role of Cytoskeleton in Apoptosis267
- I. Introduction269
- II. Actin Skeleton and Apoptosis269
- III. Intermediate Filaments275
- IV. Microtubules and Associated Proteins during Apoptosis283
- V. Cleavage of Monomeric Cytoskeletal Structures289
- VI. Conclusions290
- References290
- Chapter 11. Dietary Antioxidants and Cardiovascular Disease299
- I. Introduction299
- II. Basic Science„Oxidative Damage in Biological Systems300
- III. Role of Uncontrolled Oxidation in Atherogenesis302
- IV. Observational Epidemiology305
- V. Randomized Trials310
- VI. Conclusions315
- References316
- Chapter 12. Melatonin Receptors and Ligands321
- I. Introduction321
- II. Structure–Affinity Relationships between Melatonergic Ligands with Melatonin Receptors331
- III. Complications Involved with Generalizing about Structure–Function Relationships of the Curren346
- IV. Conclusions347
- References348
- Chapter 13. Vitamin K-Dependent Proteins355
- I. Introduction356
- II. Synthesis of Gla357
- III. Blood Coagulation Cascade359
- IV. Inhibition of Blood Coagulation362
- V. Structural Design of Vitamin K-Dependent Plasma Proteins364
- VI. Structure–Function of the Gla Domain365
- VII. Role of Membrane Binding in Coagulation373
- References379
- Chapter 14. Steroid/Nuclear Receptor Coactivators391
- I. Introduction392
- II. Identification of SRC Coactivators394
- III. Interaction with Nuclear Receptors399
- IV. X-Ray Crystal Structures405
- V. Mechanism of Transactivation417
- VI. SRC Function and Specificity426
- VII. SRC Coactivators and Human Diseases436
- VIII. Conclusions441
- References442
- Chapter 15. Thyroid Hormone Receptor, v-ErbA, and Chromatin449
- I. Introduction450
- II. Thyroid Hormone Receptor as a Stable Component of Chromatin452
- III. Transcriptional Coactivators and Corepressors for TR-RXR and v-ErbA That Modify Chromatin and R466
- IV. Insight into the Functional Roles of TR and v-ErbA in Development, Transformation, and Human Dis476
- V. Conclusions480
- References481
- Index493
Under the capable and qualified editorial leadership of Dr. Gerald Litwack, Vitamins and Hormones continues to publish cutting-edge reviews of interest to endocrinologists, biochemists, nutritionists, pharmacologists, cell biologists, and molecular biologists. First published in 1943, Vitamins and Hormones is the longest-running serial published by Academic Press. In the early days of the Serial, the subjects of vitamins and hormones were quite distinct. Now, new discoveries have proved that several of the vitamins function as hormones and many of the substances inferred by the title of the serial function in signal transduction processes. Accordingly, the Editor-in-Chief has expanded the scope of the serial to reflect this newer understanding of function-structure relationships in cellular communication. The Editorial Board now reflects expertise in the field of hormone action, vitamin action, X-ray crystal structure, physiology, and enzyme mechanisms.