Exploiting Electrode Nanoconfinement to Investigate the Catalytic Properties of Isocitrate Dehydrogenase (IDH1) and a Cancer-Associated Variant

[Image: see text] Human isocitrate dehydrogenase (IDH1) and its cancer-associated variant (IDH1 R132H) are rendered electroactive through coconfinement with a rapid NADP(H) recycling enzyme (ferredoxin-NADP(+) reductase) in nanopores formed within an indium tin oxide electrode. Efficient coupling to...

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Autores principales: Herold, Ryan A., Reinbold, Raphael, Megarity, Clare F., Abboud, Martine I., Schofield, Christopher J., Armstrong, Fraser A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273889/
https://www.ncbi.nlm.nih.gov/pubmed/34170697
http://dx.doi.org/10.1021/acs.jpclett.1c01517
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author Herold, Ryan A.
Reinbold, Raphael
Megarity, Clare F.
Abboud, Martine I.
Schofield, Christopher J.
Armstrong, Fraser A.
author_facet Herold, Ryan A.
Reinbold, Raphael
Megarity, Clare F.
Abboud, Martine I.
Schofield, Christopher J.
Armstrong, Fraser A.
author_sort Herold, Ryan A.
collection PubMed
description [Image: see text] Human isocitrate dehydrogenase (IDH1) and its cancer-associated variant (IDH1 R132H) are rendered electroactive through coconfinement with a rapid NADP(H) recycling enzyme (ferredoxin-NADP(+) reductase) in nanopores formed within an indium tin oxide electrode. Efficient coupling to localized NADP(H) enables IDH activity to be energized, controlled, and monitored in real time, leading directly to a thermodynamic redox landscape for accumulation of the oncometabolite, 2-hydroxyglutarate, that would occur in biological environments when the R132H variant is present. The technique enables time-resolved, in situ measurements of the kinetics of binding and dissociation of inhibitory drugs.
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spelling pubmed-82738892021-07-13 Exploiting Electrode Nanoconfinement to Investigate the Catalytic Properties of Isocitrate Dehydrogenase (IDH1) and a Cancer-Associated Variant Herold, Ryan A. Reinbold, Raphael Megarity, Clare F. Abboud, Martine I. Schofield, Christopher J. Armstrong, Fraser A. J Phys Chem Lett [Image: see text] Human isocitrate dehydrogenase (IDH1) and its cancer-associated variant (IDH1 R132H) are rendered electroactive through coconfinement with a rapid NADP(H) recycling enzyme (ferredoxin-NADP(+) reductase) in nanopores formed within an indium tin oxide electrode. Efficient coupling to localized NADP(H) enables IDH activity to be energized, controlled, and monitored in real time, leading directly to a thermodynamic redox landscape for accumulation of the oncometabolite, 2-hydroxyglutarate, that would occur in biological environments when the R132H variant is present. The technique enables time-resolved, in situ measurements of the kinetics of binding and dissociation of inhibitory drugs. American Chemical Society 2021-06-25 2021-07-08 /pmc/articles/PMC8273889/ /pubmed/34170697 http://dx.doi.org/10.1021/acs.jpclett.1c01517 Text en © 2021 The Authors. Published by American Chemical Society Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Herold, Ryan A.
Reinbold, Raphael
Megarity, Clare F.
Abboud, Martine I.
Schofield, Christopher J.
Armstrong, Fraser A.
Exploiting Electrode Nanoconfinement to Investigate the Catalytic Properties of Isocitrate Dehydrogenase (IDH1) and a Cancer-Associated Variant
title Exploiting Electrode Nanoconfinement to Investigate the Catalytic Properties of Isocitrate Dehydrogenase (IDH1) and a Cancer-Associated Variant
title_full Exploiting Electrode Nanoconfinement to Investigate the Catalytic Properties of Isocitrate Dehydrogenase (IDH1) and a Cancer-Associated Variant
title_fullStr Exploiting Electrode Nanoconfinement to Investigate the Catalytic Properties of Isocitrate Dehydrogenase (IDH1) and a Cancer-Associated Variant
title_full_unstemmed Exploiting Electrode Nanoconfinement to Investigate the Catalytic Properties of Isocitrate Dehydrogenase (IDH1) and a Cancer-Associated Variant
title_short Exploiting Electrode Nanoconfinement to Investigate the Catalytic Properties of Isocitrate Dehydrogenase (IDH1) and a Cancer-Associated Variant
title_sort exploiting electrode nanoconfinement to investigate the catalytic properties of isocitrate dehydrogenase (idh1) and a cancer-associated variant
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273889/
https://www.ncbi.nlm.nih.gov/pubmed/34170697
http://dx.doi.org/10.1021/acs.jpclett.1c01517
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