Slow domain reconfiguration causes power-law kinetics in a two-state enzyme

Iris Grossman-Haham, Gabriel Rosenblum, Trishool Namani, Hagen Hofmann

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Protein dynamics are typically captured well by rate equations that predict exponential decays for two-state reactions. Here, we describe a remarkable exception. The electron-transfer enzyme quiescin sulfhydryl oxidase (QSOX), a natural fusion of two functionally distinct domains, switches between open- and closed-domain arrangements with apparent power-law kinetics. Using single-molecule FRET experiments on time scales from nanoseconds to milliseconds, we show that the unusual openclose kinetics results from slow sampling of an ensemble of disordered domain orientations. While substrate accelerates the kinetics, thus suggesting a substrate-induced switch to an alternative free energy landscape of the enzyme, the power-law behavior is also preserved upon electron load. Our results show that the slow sampling of open conformers is caused by a variety of interdomain interactions that imply a rugged free energy landscape, thus providing a generic mechanism for dynamic disorder in multidomain enzymes.

Original languageEnglish
Pages (from-to)513-518
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number3
StatePublished - 16 Jan 2018
Externally publishedYes


  • Enzyme dynamics
  • Memory effects
  • Protein disorder
  • Single-molecule FRET
  • Subdiffusion


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