The Hydricity and Reactivity Relationship in [ FeFe ]-hydrogenases

Abstract

Reactivity of transition metal catalysts is controlled by covalent and non-covalent interactions that tune thermodynamic properties including hydricity. Hydricity is critical to catalytic activity and for modulating the reduction or oxidation of chemical compounds. Likewise, enzymes can employ transition metal cofactors and use metal-hydride intermediates tuned by protein frameworks to selectively control reactivity. One example, the [FeFe]-hydrogenases, catalyze reversible H2 activation with H2 oxidation to H+ reduction ratios spanning ~107 in rate, offering a model to determine the extent that hydricity controls reactivity. To address this question, the hydricity of the catalytic H cluster of two [FeFe]-hydrogenases, CpI and CpII, were compared. We show that for CpI, the higher rates of H+ reduction correspond to a more hydridic H cluster, whereas CpII, which strongly favors H2 oxidation, has a less hydridic H cluster. The results demonstrate that enzymes manipulate metal cofactor hydricity to enable an extraordinary range of chemical reactivity.

Editorial: Hydrogenase: structure, function, maturation, and application

“…In the realm of structurefunction relationships, Kisgeropoulos et al investigated the effect of amino acid exchanges of the primary proteinaceous proton acceptor in [FeFe]-hydrogenase. The data expand previous work (Cornish et al, 2011;Morra et al, 2012;Duan et al, 2018;Artz et al, 2020), demonstrating that the pK a of the proton acceptor is one factor controlling the catalytic bias of the enzyme. Three further articles dealt with functional aspects of hydrogenases.…”

The Contribution of Proton-Donor pKa on Reactivity Profiles of [FeFe]-hydrogenases

“…Using redox-dye mediated assays on the purified CrHydA1 C169S variant, H 2 oxidation and evolution activities were determined and compared to CaI C298S (Cornish et al, 2011) and CpII C169S (Artz et al, 2020a; Table 2). The reactivity results show a collective shift toward H 2 oxidation reactivity for all the enzymes.…”