guanosine-diphosphate and Carcinogenesis

Ras-related C3 botulinum toxin substrate 1 (Rac1) plays critical roles in the maintenance of cell morphology by cycling between inactive guanosine diphosphate (GDP)-bound and active guanosine triphosphate (GTP)-bound states. Rac1 P29S mutant is known to strongly promote oncogenesis by facilitating its intrinsic GDP dissociation and thereby increasing the level of the GTP-bound state. Here, we used solution nuclear magnetic resonance spectroscopy to investigate the activation mechanism of the oncogenic P29S mutant. We demonstrate that the conformational landscape is markedly altered in the mutant, and the preexisting equilibrium is shifted toward the conformation with reduced affinity for Mg

Topics: Amino Acid Substitution; Binding Sites; Carcinogenesis; Cations, Divalent; Cloning, Molecular; Coenzymes; Escherichia coli; Gene Expression; Genetic Vectors; Glutathione Transferase; Guanosine Diphosphate; Guanosine Triphosphate; Humans; Kinetics; Magnesium; Models, Molecular; Mutation; Neoplasm Proteins; Nuclear Magnetic Resonance, Biomolecular; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; rac1 GTP-Binding Protein; Recombinant Fusion Proteins; Thermodynamics