Tuning Catalytic Bias of Hydrogen Gas Producing Hydrogenases

Jacob H. Artz, Oleg A. Zadvornyy, David W. Mulder, Stephen M. Keable, Aina E. Cohen, Michael W. Ratzloff, S. Garrett Williams, Bojana Ginovska, Neeraj Kumar, Jinhu Song, Scott E. McPhillips, Catherine M. Davidson, Artem Y. Lyubimov, Natasha Pence, Gerrit J. Schut, Anne K. Jones, S. Michael Soltis, Michael W.W. Adams, Simone Raugei, Paul W. KingJohn W. Peters

Research output: Contribution to journalArticlepeer-review

50 Scopus Citations


Hydrogenases display a wide range of catalytic rates and biases in reversible hydrogen gas oxidation catalysis. The interactions of the iron-sulfur-containing catalytic site with the local protein environment are thought to contribute to differences in catalytic reactivity, but this has not been demonstrated. The microbe Clostridium pasteurianum produces three [FeFe]-hydrogenases that differ in "catalytic bias" by exerting a disproportionate rate acceleration in one direction or the other that spans a remarkable 6 orders of magnitude. The combination of high-resolution structural work, biochemical analyses, and computational modeling indicates that protein secondary interactions directly influence the relative stabilization/destabilization of different oxidation states of the active site metal cluster. This selective stabilization or destabilization of oxidation states can preferentially promote hydrogen oxidation or proton reduction and represents a simple yet elegant model by which a protein catalytic site can confer catalytic bias.

Original languageAmerican English
Pages (from-to)1227-1235
Number of pages9
JournalJournal of the American Chemical Society
Issue number3
StatePublished - 2020

Bibliographical note

Publisher Copyright:
© 2019 American Chemical Society.

NREL Publication Number

  • NREL/JA-2700-74582


  • catalytic bias
  • hydrogen
  • hydrogenases


Dive into the research topics of 'Tuning Catalytic Bias of Hydrogen Gas Producing Hydrogenases'. Together they form a unique fingerprint.

Cite this