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


Researchers in biochemistry, molecular and cell biology, pharmacology, and cancer

Table of Contents

Chapter One. The Ras Superfamily G-Proteins

1 The Ras Superfamily G-Proteins

2 Overview of Structure, Activity, and Regulatory Proteins

3 Upstream and Downstream Signaling Pathways

4 Significance in Human Cancer

5 Strategies to Inhibit the Ras Superfamily G-Proteins



Chapter Two. NMR Study to Identify a Ligand-Binding Pocket in Ras

1 KRAS as a Drug Target

2 Nuclear Magnetic Resonance Fragment Screen

3 Protein Ligand Co-structures

4 Inhibition of SOS1-Mediated Nucleotide Exchange for RAS

5 Ligand-Binding Sites on Ras

6 Summary and Conclusions


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 Molecules

7 Mapping the Binding Site Hot Spots in Ras: Targeting the Protein/Membrane Interface

8 Conclusions


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


Chapter Five. Sugar-Based Inhibitors of Ras Activation: Biological Activity and Identification of Ras–Inhibitor Binding Interface

1 Introduction

2 Initial Compound


No. of pages:
© 2013
Academic Press
eBook ISBN:
Print ISBN:

About the serial-volume-editor

Fuyuhiko Tamanoi

Professor Fuyu Tamanoi works at the Dept. of Microbiology, Immunology and Molecular Genetics at the University of California.

Affiliations and Expertise

University of California, Los Angeles, USA