NMR 1H,13C, 15N resonance assignment of the G12C mutant of human K-Ras bound to GppNHp

K-Ras exists in two distinct structural conformations specific to binding of GDP and GTP nucleotides. The cycling between an inactive, GDP-bound state and an active, GTP-bound state is regulated by guanine nucleotide exchange factors and GTPase activating proteins, respectively. The activated form of K-Ras regulates cell proliferation, differentiation and survival by controlling several downstream signaling pathways. Oncogenic mutations that attenuate the GTPase activity of K-Ras result in accumulation of this key signaling protein in its hyperactivated state, leading to uncontrolled cellular proliferation and tumorogenesis. Mutations at position 12 are the most prevalent in K-Ras associated cancers, hence K-Ras G12C has become a recent focus of research for therapeutic intervention. Here we report 1 H N, 15 N, and 13 C backbone and 1 H, 13 C side-chain resonance assignments for the 19.3 kDa (aa 1–169) human K-Ras protein harboring an oncogenic G12C mutation in the active GppNHp-bound form (K-Ras G12C-GppNHp ), using heteronuclear, multidimensional NMR spectroscopy at 298K. Triple-resonance data assisted the assignments of the backbone 1 H, 15 N, and 13 C resonances of 126 out of 165 non-proline residues. The vast majority of unassigned residues are exchange-broadened beyond detection on the NMR time scale and belong to the P-loop and two flexible Switch regions.