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

2 Scopus citations

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.",

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

author = "Mayukh Chakrabarti and Gabelli, {Sandra B.} and Amzel, {L. Mario}",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",

year = "2020",

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doi = "10.1016/j.str.2020.01.010",

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AU - Chakrabarti, Mayukh

AU - Gabelli, Sandra B.

AU - Amzel, L. Mario

PY - 2020/4/7

Y1 - 2020/4/7

N2 - 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.

AB - 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.

KW - catalytic mechanism

KW - dynamic allostery

KW - enzyme activation

KW - molecular dynamics

KW - phosphoinositide (3,4,5)-trisphosphate

KW - phosphoinositide (4,5)-bisphosphate

KW - phosphoinositide kinase

KW - population increase

KW - signaling pathway

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SP - 465-474.e5

JO - Structure

JF - Structure

IS - 4

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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