Allosteric Activation of PI3Kα Results in Dynamic Access to Catalytically Competent Conformations

Mayukh Chakrabarti; Sandra B Gabelli; L. Mario Amzel

doi:10.1016/j.str.2020.01.010

Allosteric Activation of PI3Kα Results in Dynamic Access to Catalytically Competent Conformations

Mayukh Chakrabarti, Sandra B Gabelli, L. Mario Amzel

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

PI3Kα is a phospholipid kinase that phosphorylates PIP₂ to generate PIP₃, a scaffold for many important downstream signaling pathways. In this paper, Chakrabarti et al. demonstrate that dynamic allostery can increase the population of PI3Kα states compatible with catalysis, which has implications for the development of new PI3K therapeutics.

Original language	English (US)
Pages (from-to)	465-474.e5
Journal	Structure
Volume	28
Issue number	4
DOIs	https://doi.org/10.1016/j.str.2020.01.010
State	Published - Apr 7 2020

Keywords

catalytic mechanism
dynamic allostery
enzyme activation
molecular dynamics
phosphoinositide (3,4,5)-trisphosphate
phosphoinositide (4,5)-bisphosphate
phosphoinositide kinase
population increase
signaling pathway

ASJC Scopus subject areas

Structural Biology
Molecular Biology

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10.1016/j.str.2020.01.010

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title = "Allosteric Activation of PI3Kα Results in Dynamic Access to Catalytically Competent Conformations",

abstract = "PI3Kα is a phospholipid kinase that phosphorylates PIP2 to generate PIP3, a scaffold for many important downstream signaling pathways. In this paper, Chakrabarti et al. demonstrate that dynamic allostery can increase the population of PI3Kα states compatible with catalysis, which has implications for the development of new PI3K therapeutics.",

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KW - signaling pathway

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