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Volume 10, Issue 8 (Suppl) J Proteomics Bioinform, an open access journal
ISSN: 0974-276X Structural Biology 2017
September 18-20, 2017
9th International Conference on
Structural Biology
September 18-20, 2017 Zurich, Switzerland
Hagen Hofmann et al., J Proteomics Bioinform 2017, 10:8(Suppl)
DOI: 10.4172/0974-276X-C1-0100
Slow domain reconfiguration causes power law kinetics in a two-state enzyme
Hagen Hofmann, Iris Grossman Haham, Gabriel Rosenblum and Trishool Namani
Weizmann Institute of Science, Israel
Conformational transitions in proteins are typically captured well by rate equations that predict exponential kinetics 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 Foerster resonance energy transfer (FRET) experiments on timescales
from nanoseconds to milliseconds, we showed that the unusual open-close kinetics results from slow domain rearrangements
in a heterogeneous ensemble of open conformers. 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 conformational multiplicity with slow sampling dominates the motions of QSOX, thus providing an
explanation for catalytic memory effects in other enzymes.
Biography
Hagen Hofmann received his PhD from the Martin Luther University Halle-Wittenberg (Germany) in 2008. In the period 2008 - 2014, he was a Postdoctoral Fellow
at the University of Zurich in the group of Benjamin Schuler and since 2014 he is heading the “Molecular Systems Biophysics” group at the Weizmann Institute of
Science (Israel). He and his group use a broad set of single-molecule fluorescence tools to understand the dynamics of proteins and protein networks on timescales
from nanoseconds to hours. In addition, live-cell imaging, in vivo single-molecule FRET, and single particle tracking is used to monitor proteins in live cells. His
interest ranges from the physics of disordered proteins over coupled binding and folding reactions up to stochastic genetic circuits and regulatory protein networks.