Experimental and theoretical study of the reaction of FeFe hydrogenases with dioxygen

Hydrogenases are enzymes that catalyze hydrogen oxidation and production. The so-called "FeFe hydrogenases", the active site of which is a [Fe6(CN)2(CO)3] cluster, are particularly efficient. Their inhibition by O2 prevents them from being used for H2 production. Combining electrochemical experiments, site-directed mutagenesis, molecular dynamics calculations and quantum chemistry calculations allowed to elucidate all steps of the reaction with O2 and to predict the rate of inhibition. These results will pave the way for engineering enzymes that resist O2.