Fig. 1: The unusual O2-resistance of [FeFe]-hydrogenase CbA5H.

The H-cluster of CpI and other [FeFe]-hydrogenases is irreversibly destroyed when exposed to O2. CbA5H is a rare exception, as it reversibly converted into an inactive but O2-protected state (Hinact), even in the absence of exogenous sulfide. From the O2-protected state, CbA5H can be reactivated by reduction under anaerobic conditions. ROS: reactive O2-species resulting from O2-activation after Fed-binding. Green bar: unknown feature or mechanism, protecting the H-cluster of CbA5H from O2-attack in Hinact.