Reduced dynamic complexity allows structure elucidation of an excited state of KRAS^G13D.

ABSTRACT: Localized dynamics of RAS, including regions distal to the nucleotide-binding site, is of high interest for elucidating the mechanisms by which RAS proteins interact with effectors and regulators and for designing inhibitors. Among several oncogenic mutants, methyl relaxation dispersion experiments reveal highly synchronized conformational dynamics in the active (GMPPNP-bound) KRAS^G13D, which suggests an exchange between two conformational states in solution. Methyl and ³¹P NMR spectra of active KRAS^G13D in solution confirm a two-state ensemble interconverting on the millisecond timescale, with a major P^γ atom peak corresponding to the dominant State 1 conformation and a secondary peak indicating an intermediate state different from the known Sta

SUBMITTER: Chao FA 

PROVIDER: S-EPMC10238545 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature