Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.


Issue 13, 2020
Previous Article Next Article

Unravelling the effect of the E545K mutation on PI3Kα kinase

Author affiliations

Abstract

PI3Kα controls several cellular processes and its aberrant signalling is implicated in tumorigenesis. One of its hotspot mutations, E545K, increases PI3Kα lipid kinase activity, but its mode of action is only partially understood. Here, we perform biased and unbiased molecular dynamics simulations of PI3Kα and uncover, for the first time, the free energy landscape of the E545K PI3Kα mutant. We reveal the mechanism by which E545K leads to PI3Kα activation in atomic-level detail, which is considerably more complex than previously thought.

Graphical abstract: Unravelling the effect of the E545K mutation on PI3Kα kinase

Back to tab navigation

Supplementary files

Article information


Submitted
20 Nov 2019
Accepted
26 Feb 2020
First published
26 Feb 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020,11, 3511-3515
Article type
Edge Article

Unravelling the effect of the E545K mutation on PI3Kα kinase

I. Galdadas, F. L. Gervasio and Z. Cournia, Chem. Sci., 2020, 11, 3511
DOI: 10.1039/C9SC05903B

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

Reproduced material should be attributed as follows:

  • For reproduction of material from NJC:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
  • For reproduction of material from PCCP:
    [Original citation] - Published by the PCCP Owner Societies.
  • For reproduction of material from PPS:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
  • For reproduction of material from all other RSC journals:
    [Original citation] - Published by The Royal Society of Chemistry.

Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.


Social activity

Search articles by author

Spotlight

Advertisements