Electron transfer activation of a second water channel for proton transport in [FeFe]-hydrogenase

• Published in: The Journal of chemical physics Vol. 141; no. 22; p. 22D527
• Main Authors: Sode, Olaseni, Voth, Gregory A
• Format: Journal Article
• Language: English
• Published: United States 14.12.2014
• Subjects: Aquaporins - chemistry; Aquaporins - metabolism; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Clostridium - chemistry; Clostridium - metabolism; Electron Transport; Hydrogenase - chemistry; Hydrogenase - metabolism; Iron-Sulfur Proteins - chemistry; Iron-Sulfur Proteins - metabolism; Molecular Dynamics Simulation; Protons; Thermodynamics
• ISSN: 1089-7690
• DOI: 10.1063/1.4902236

Hydrogenase enzymes are important because they can reversibly catalyze the production of molecular hydrogen. Proton transport mechanisms have been previously studied in residue pathways that lead to the active site of the enzyme via residues Cys299 and Ser319. The importance of this pathway and these residues has been previously exhibited through site-specific mutations, which were shown to interrupt the enzyme activity. It has been shown recently that a separate water channel (WC2) is coupled with electron transport to the active site of the [FeFe]-hydrogenase. The water-mediated proton transport mechanisms of the enzyme in different electronic states have been studied using the multistate empirical valence bond reactive molecular dynamics method, in order to understand any role WC2 may have in facilitating the residue pathway in bringing an additional proton to the enzyme active site. In a single electronic state A(2-), a water wire was formed through which protons can be transported with a low free energy barrier. The remaining electronic states were shown, however, to be highly unfavorable to proton transport in WC2. A double amino acid substitution is predicted to obstruct proton transport in electronic state A(2-) by closing a cavity that could otherwise fill with water near the proximal Fe of the active site.