Exploiting Electrode Nanoconfinement to Investigate the Catalytic Properties of Isocitrate Dehydrogenase (IDH1) and a Cancer-Associated Variant
Ryan A. Herold, Raphael Reinbold, Clare F. Megarity, Martine I. Abboud, Christopher J. Schofield, Fräser A. Armstrong
Abstract
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.
Topics & Concepts
Isocitrate dehydrogenaseIDH1ChemistryDissociation (chemistry)KineticsDehydrogenaseElectrodeRedoxEnzymeBiochemistryBiophysicsInorganic chemistryBiologyPhysical chemistryPhysicsQuantum mechanicsGeneMutationAdvanced biosensing and bioanalysis techniquesNanopore and Nanochannel Transport StudiesGraphene research and applications