http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-2.xsd
Inhibitors of the Ras superfamily g-proteins
1 online resource (361 pages) : illustrations (some color)
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 the latest developments in the field.
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
Includes bibliographical references and indexes.
Inhibitors of the Ras superfamily g-proteins. Part A