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Inhibitors of the Ras superfamily g-proteins. Part A /
This special volume of The Enzymes is targeted toward researchers in biochemistry, molecular and cell biology, pharmacology, and cancer. This thematic volume discusses inhibitors of the Ras superfamily G-proteins. Key features: * Contributions from leading authorities * Informs and updates on all th...
| Clasificación: | Libro Electrónico |
|---|---|
| Otros Autores: | |
| Formato: | Electrónico eBook |
| Idioma: | Inglés |
| Publicado: |
Waltham, MA :
Academic Press,
2013.
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| Edición: | First edition. |
| Colección: | Enzymes ;
v. 33. |
| Temas: | |
| Acceso en línea: | Texto completo Texto completo |
Tabla de Contenidos:
- Front Cover; Inhibitors of the Ras Superfamily G-proteins, Part A; Copyright; Contents; Preface; Chapter One: The Ras Superfamily G-Proteins; 1. The Ras Superfamily G-Proteins; 2. Overview of Structure, Activity, and Regulatory Proteins; 2.1. Three-dimensional structure; 2.2. GEF and GAP regulate the activities of the Ras superfamily G-proteins; 2.3. Posttranslational modification and membrane association; 3. Upstream and Downstream Signaling Pathways; 4. Significance in Human Cancer; 5. Strategies to Inhibit the Ras Superfamily G-Proteins; Acknowledgments; References
- Chapter Two: NMR Study to Identify a Ligand-Binding Pocket in Ras1. KRAS as a Drug Target; 2. Nuclear Magnetic Resonance Fragment Screen; 2.1. Introduction; 2.2. The design of NMR fragment-screening cascade against KRas4B G12D mutant; 2.3. The fragment library; 2.4. The ligand-based primary screen; 2.5. Hit validation using protein-observed NMR; 2.6. FH2L using Kd determinations based on protein-observed NMR; 3. Protein Ligand Co-structures; 3.1. The crystal structure of KRas4BG12D (KRasm); 3.2. The high-resolution view of ligand and KRasm interaction
- 3.3. The ligand-binding pocket expands upon DCAI binding4. Inhibition of SOS1-Mediated Nucleotide Exchange for RAS; 5. Ligand-Binding Sites on Ras; 6. Summary and Conclusions; References; Chapter Three: The Allosteric Switch and Conformational States in Ras GTPase Affected by Small Molecules; 1. Introduction; 2. Ras Architecture: The G Domain and Its Function; 3. The Allosteric Switch in Ras-GTP and Its Role in Intrinsic Hydrolysis; 4. The Allosteric Switch Linked to the Ras/Raf/MEK/ERK Pathway; 5. Most Ras Structures in the Protein Data Bank are in the R State
- 6. Modulation of the Allosteric States in Ras-GTP by Small Molecules7. Mapping the Binding Site Hot Spots in Ras: Targeting the Protein/Membrane Interface; 8. Conclusions; References; Chapter Four: State 1(T) Inhibitors of Activated Ras; 1. Introduction; 2. Allosteric Regulation of the Ras-Effector Interaction; 3. Identification of State 1(T) in Activated Ras by NMR Spectroscopy; 4. Identification of 1(T) Inhibitors by NMR Spectroscopy; 5. Metal-Cyclen Derivatives as 1(T) Inhibitors; 6. Metal-BPA Derivatives as 1(T) Inhibitors; 7. Outlook: Possible Applications to Other Small GTPases