Galdadas, I;
Gervasio, FL;
Cournia, Z;
(2020)
Unravelling the effect of the E545K mutation on PI3Kα kinase.
Chemical Science
, 11
pp. 3511-3515.
10.1039/c9sc05903b.
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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.
| Type: | Article |
|---|---|
| Title: | Unravelling the effect of the E545K mutation on PI3Kα kinase |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1039/c9sc05903b |
| Publisher version: | https://doi.org/10.1039/c9sc05903b |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence (http://creativecommons.org/licenses/by-nc/3.0/). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10093543 |
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