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Hagen Hofmann

Hagen Hofmann

Weizmann Institute of Science, Israel

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

Biography

Biography: Hagen Hofmann

Abstract

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 show 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.

References:

  1. Grossman, I. et al. (2015) Single-molecule spectroscopy exposes hidden states in an enzymatic electron relay. Nature Communications 6:1-10.
  2. Hofmann, H (2016). Speedy Motion For Function.  Nature Chemical Biology. 12:576-577.
  3. Schuler, B; Soranno, A; Hofmann, H; Nettels, D (2016). Single-Molecule Fret Spectroscopy and the Polymer Physics of Unfolded and Intrinsically Disordered Proteins.  Annual Review of Biophysics. 45:207-231.
  4. Hofmann, H; Soranno, A; Borgia, A; Gast, K; Nettels, D; Schuler, B (2012). Polymer Scaling Laws of Unfolded and Intrinsically Disordered Proteins Quantified With Single-Molecule Spectroscopy.  Proceedings of the National Academy of Sciences of the United States of America. 109:16155-16160.

5.   Hofmann, H; Hillger, F; Pfeil, Sh; Hoffmann, A; Streich, D; Haenni, D; Nettels, D; Lipman, Ea; Schuler, B (2010). Single-Molecule Spectroscopy of Protein Folding in a Chaperonin Cage.  Proceedings of the National Academy of Sciences of the United States of America. 107:11793-11798.