TY - JOUR
T1 - Slow domain reconfiguration causes power-law kinetics in a two-state enzyme
AU - Grossman-Haham, Iris
AU - Rosenblum, Gabriel
AU - Namani, Trishool
AU - Hofmann, Hagen
N1 - Publisher Copyright:
© 2018 National Academy of Sciences.
PY - 2018/1/16
Y1 - 2018/1/16
N2 - 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.
AB - 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.
KW - Enzyme dynamics
KW - Memory effects
KW - Protein disorder
KW - Single-molecule FRET
KW - Subdiffusion
UR - http://www.scopus.com/inward/record.url?scp=85042135977&partnerID=8YFLogxK
U2 - 10.1073/pnas.1714401115
DO - 10.1073/pnas.1714401115
M3 - Article
C2 - 29298911
AN - SCOPUS:85042135977
SN - 0027-8424
VL - 115
SP - 513
EP - 518
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 3
ER -