Structural Perturbations due to Mutation (H1047R) in Phosphoinositide-3-kinase (PI3Kα) and Its Involvement in Oncogenesis: An in Silico Insight.

ABSTRACT: PI3Kα is a heterodimer protein consisting of two subunits (p110α and p85α) which promotes various signaling pathways. Oncogenic mutation in the catalytic subunit p110α of PI3Kα at the 1047 position in the kinase domain substitutes the histidine with arginine. This mutation brings about conformational transitions in the protein complex. These transitions expose the membrane binding region of PI3Kα, and then it independently binds to the cell membrane through its kinase domain without the involvement of the membrane-bound protein RAS. We observed notable changes between the protein complexes (p110α-p85α) of native and mutant structures at the atomic level using molecular dynamics simulations. Simulation results revealed formation of a less number of hydrogen bonds between the two subunits in

SUBMITTER: Sharma J 

PROVIDER: S-EPMC6776984 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature