Can enzyme proximity accelerate cascade reactions?

Andrij Kuzmak, Sheiliza Carmali, Eric von Lieres, Alan J Russell, Svyatoslav Kondrat

Research output: Contribution to journalArticle

18 Citations (Scopus)
2 Downloads (Pure)

Abstract

The last decade has seen an exponential expansion of interest in conjugating multiple enzymes of cascades in close proximity to each other, with the overarching goal being to accelerate the overall reaction rate. However, some evidence has emerged that there is no effect of proximity channeling on the reaction velocity of the popular GOx-HRP cascade, particularly in the presence of a competing enzyme (catalase). Herein, we rationalize these experimental results quantitatively. We show that, in general, proximity channeling can enhance reaction velocity in the presence of competing enzymes, but in steady state a significant enhancement can only be achieved for diffusion-limited reactions or at high concentrations of competing enzymes. We provide simple equations to estimate the effect of channeling quantitatively and demonstrate that proximity can have a more pronounced effect under crowding conditions in vivo, particularly that crowding can enhance the overall rates of channeled cascade reactions.

Original languageEnglish
Article number455
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 24 Jan 2019
Externally publishedYes

Keywords

  • Algorithms
  • Binding, Competitive
  • Catalase/metabolism
  • Diffusion
  • Glucose Oxidase/metabolism
  • Horseradish Peroxidase/metabolism
  • Hydrogen Peroxide/metabolism
  • Kinetics
  • Models, Theoretical
  • Protein Binding
  • Pittsburgh

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