Exploiting Electrode Nanoconfinement to Investigate the Catalytic Properties of Isocitrate Dehydrogenase (IDH1) and a Cancer-Associated Variant.
J Phys Chem Lett
; 12(26): 6095-6101, 2021 Jul 08.
Article
em En
| MEDLINE
| ID: mdl-34170697
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Nanotecnologia
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Enzimas
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Isocitrato Desidrogenase
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Mutação
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Neoplasias
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article