Catalytically Competent Non-transforming H-RAS^G12P Mutant Provides Insight into Molecular Switch Function and GAP-independent GTPase Activity of RAS.

ABSTRACT: RAS mutants have been extensively studied as they are associated with development of cancer; however, H-RAS^G12P mutant has remained untouched since it does not lead to transformation in the cell. To the best of our knowledge, this is the first study where structural/dynamical properties of H-RAS^G12P have been investigated -in comparison to H-RAS^WT, H-RAS^G12D, RAF-RBD-bound and GAP-bound H-RAS^WT- using molecular dynamics simulations (total of 9 μs). We observed remarkable differences in dynamics of Y32. Specifically, it is located far from the nucleotide binding pocket in the catalytically-active GAP-bound H-RAS^WT, whereas it makes close interaction with the nucleotide in signaling-active systems (H-RAS^G12D, KRAS4B

SUBMITTER: Ilter M 

PROVIDER: S-EPMC6662853 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature