PNNL

Abstract

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 reactivity but this has not been demonstrated. The microbe Clostridium pasteurianum produces three [FeFe]-hydrogenases that differ in their “catalytic bias” exerting a disproportionate rate acceleration in one direction or the other spanning a remarkable 7-orders of magnitude. The combination of high-resolution structural work, biochemical analyses, and computational modeling demonstrate the catalytic bias can be explained through a simple yet elegant model involving the relative stabilization and destabilization of different states of the catalytic active site metal cluster through protein secondary interactions allowing it to operate under different reduction-oxidation regimes.