NMR H,C, N backbone and C side chain resonance assignment of the G12C mutant of human K-Ras bound to GDP.

Biomol NMR Assign

Warp Drive Bio, Inc., 400 Technology Square, Cambridge, MA, 02139, USA.

Published: October 2018

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Article Abstract

K-Ras is a key driver of oncogenesis, accounting for approximately 80% of Ras-driven human cancers. The small GTPase cycles between an inactive, GDP-bound and an active, GTP-bound state, regulated by guanine nucleotide exchange factors and GTPase activating proteins, respectively. Activated K-Ras regulates cell proliferation, differentiation and survival by signaling through several effector pathways, including Raf-MAPK. Oncogenic mutations that impair the GTPase activity of K-Ras result in a hyperactivated state, leading to uncontrolled cellular proliferation and tumorogenesis. A cysteine mutation at glycine 12 is commonly found in K-Ras associated cancers, and has become a recent focus for therapeutic intervention. We report here HN, and C resonance assignments for the 19.3 kDa (aa 1-169) human K-Ras protein harboring an oncogenic G12C mutation in the GDP-bound form (K-RAS), using heteronuclear, multidimensional NMR spectroscopy. Backbone H-N correlations have been assigned for all non-proline residues, except for the first methionine residue.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132845PMC
http://dx.doi.org/10.1007/s12104-018-9821-8DOI Listing

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