Insights into the mechanism of the PIK3CA E545K activating mutation using MD simulations.

ABSTRACT: Phosphoinositide 3-kinase alpha (PI3Kα) is involved in fundamental cellular processes including cell proliferation and differentiation and is frequently mutated in human malignancies. One of the most common mutations is E545K, which results in an amino acid substitution of opposite charge. It has been recently proposed that in this oncogenic charge-reversal mutation, the interactions between the protein catalytic and regulatory subunits are abrogated, resulting in loss of regulation and constitutive PI3Kα activity, which can lead to oncogenesis. To assess the mechanism of the PI3Kα E545K activating mutation, extensive Molecular Dynamics simulations were performed to examine conformational changes differing between the wild type (WT) and mutant proteins as they occur in microsecond simulati

SUBMITTER: Leontiadou H 

PROVIDER: S-EPMC6195558 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature