A novel carcinogenic PI3Kα mutation suggesting the role of helical domain in transmitting nSH2 regulatory signals to kinase domain

Mutations in PIK3CA, which encodes p110α subunit of PI3K class IA enzymes, are highly frequent breast cancer. Here, we aimed to probe mutations exon 9 PIK3CA and computationally simulate their function. PCR/HRM PCR/sequencing were used for mutation detection 40 cancer specimens. The identified queried via silico algorithms check the pathogenicity. molecular dynamics (MD) simulations utilized assess function mutant proteins. Three samples found harbor at least one E542K, E545K L551Q has not been reported previously. All confirmed be pathogenic MD revealed impact on protein regulation. novel was similar that previously carcinogenic mutants, E542K E545K. A functional role helical domain also suggested by inhibitory signal p85α is conducted kinase domain. Helical lead impairment allosteric Interestingly, our results show substrate binding pocket mutants may have differential affinity enzyme substrates, including anit-p110α drugs. could feature known mutations.