A QM/MM study of proton transport pathways in a [NiFe] hydrogenase

Galván, Ignacio Fdez.; Volbeda, Anne; Fontecilla‐Camps, Juan C.; Field, Martin J.

doi:10.1002/prot.22045

Cited by 60 publications

(18 citation statements)

References 43 publications

(48 reference statements)

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“…Consequently, Glu18 is likely to be part of the proton transfer pathway. Several theoretical studies were performed to confirm this Glu18 related route and to identify another possible proton pathways [18], [24], [25]. All these proposed routes were described using 3D structure of [NiFe] hydrogenases belonging to sulfate-reducing bacteria of Desulfovibrio genus.…”

Section: Discussionmentioning

confidence: 94%

“…Theoretical [24], [25] and experimental studies [26] attempted to identify the residues involved in the proton translocation. Thus, biochemical and biophysical analysis of the Glu18Gln mutant of the D. fructosovorans enzyme ( Desulfovibrio gigas numbering; Glu18 corresponds to Glu25 in D. fructosovorans ) indicated the essential role of the conserved Glu18 in proton transfer, as inferred from the crystallographic data [26].…”

Section: Introductionmentioning

confidence: 99%

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Analyses of the Large Subunit Histidine-Rich Motif Expose an Alternative Proton Transfer Pathway in [NiFe] Hydrogenases

et al. 2012

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A highly conserved histidine-rich region with unknown function was recognized in the large subunit of [NiFe] hydrogenases. The HxHxxHxxHxH sequence occurs in most membrane-bound hydrogenases, but only two of these histidines are present in the cytoplasmic ones. Site-directed mutagenesis of the His-rich region of the T. roseopersicina membrane-attached Hyn hydrogenase disclosed that the enzyme activity was significantly affected only by the replacement of the His104 residue. Computational analysis of the hydrogen bond network in the large subunits indicated that the second histidine of this motif might be a component of a proton transfer pathway including Arg487, Asp103, His104 and Glu436. Substitutions of the conserved amino acids of the presumed transfer route impaired the activity of the Hyn hydrogenase. Western hybridization was applied to demonstrate that the cellular level of the mutant hydrogenases was similar to that of the wild type. Mostly based on theoretical modeling, few proton transfer pathways have already been suggested for [NiFe] hydrogenases. Our results propose an alternative route for proton transfer between the [NiFe] active center and the surface of the protein. A novel feature of this model is that this proton pathway is located on the opposite side of the large subunit relative to the position of the small subunit. This is the first study presenting a systematic analysis of an in silico predicted proton translocation pathway in [NiFe] hydrogenases by site-directed mutagenesis.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Analyses of the Large Subunit Histidine-Rich Motif Expose an Alternative Proton Transfer Pathway in [NiFe] Hydrogenases

et al. 2012

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“…This effectively provides two sites for deprotonation, and may contribute to the high efficiency for this reversible process. Multiple proton channels have been proposed for both [FeFe]-and [NiFe]-hydrogenases (22)(23)(24)(25)(26), and it may be that the enzymes use multiple channels to achieve maximum efficiency. Structural studies and studies evaluating the movement of protons are ongoing to provide additional details of the mechanism for the protonated complex.…”

Section: Discussionmentioning

confidence: 99%

Amino acid modified Ni catalyst exhibits reversible H ₂ oxidation/production over a broad pH range at elevated temperatures

Dutta

DuBois

Roberts

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

116

137

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Hydrogenases interconvert H 2 and protons at high rates and with high energy efficiencies, providing inspiration for the development of molecular catalysts. Studies designed to determine how the protein scaffold can influence a catalytically active site have led to the synthesis of amino acid derivatives of [Ni(P 2+ (CyAA). It is shown that theseCyAA derivatives can catalyze fully reversible H 2 production/ oxidation at rates approaching those of hydrogenase enzymes. The reversibility is achieved in acidic aqueous solutions (pH = 0-6), 1 atm 25% H 2 /Ar, and elevated temperatures (tested from 298 to 348 K) for the glycine (CyGly), arginine (CyArg), and arginine methyl ester (CyArgOMe) derivatives. As expected for a reversible process, the catalytic activity is dependent upon H 2 and proton concentrations. CyArg is significantly faster in both directions (∼300 s −1 H 2 production and 20 s −1 H 2 oxidation; pH = 1, 348 K, 1 atm 25% H 2 /Ar) than the other two derivatives. The slower turnover frequencies for CyArgOMe (35 s −1 production and 7 s −1 oxidation under the same conditions) compared with CyArg suggests an important role for the COOH group during catalysis. That CyArg is faster than CyGly (3 s −1 production and 4 s −1 oxidation) suggests that the additional structural features imparted by the guanidinium groups facilitate fast and reversible H 2 addition/release. These observations demonstrate that outer coordination sphere amino acids work in synergy with the active site and can play an important role for synthetic molecular electrocatalysts, as has been observed for the protein scaffold of redox active enzymes.hydrogenase mimics | reversible catalysis | amino acid catalysts | outer coordination sphere | homogeneous electrocatalysis H ydrogenases are metalloenzymes that interconvert H 2 and protons (Eq. 1), reactions necessary for biological processes within certain organisms to provide energy by splitting hydrogen, as well as to balance the redox potential in the cell (1-4). Their reversible catalytic behavior is a demonstration of their energy efficiency, indicating that they are operating at the equilibrium potential of the H 2 /H + couple. They are also very active under conditions optimized for a particular direction, operating at up to 20,000 s −1 for H 2 production (5) and 10,000 s −1 for H 2 oxidation (6). Under conditions where reversibility is optimized (3, 7-10), net turnover frequencies (TOFs) are typically slower. For hydrogenases attached to electrode surfaces, the TOFs are not always quantitated due to uncertainty in surface coverage (9), but in one example, TOFs for a series of mutants of Desulfovibrio fructosovorans [NiFe]-hydrogenase were reported, ranging from 3 to 500 s −1 for H 2 production and 600 to 1,000 s −1 for H 2 oxidation under one set of conditions (8).The ability of hydrogenases to function reversibly requiring no applied overpotential and with high catalytic TOFs is a direct reflection of their biological optimization, and a hallmark of enzymes. Reversibility requires enzym...

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“…67 Note that, as we mentioned earlier, during the all-atom simulations, Glu25 L forms a network with rigid residues Glu16 S and Glu75 S (see Figure 2) which are involved in a proton transfer pathway from the active site to the molecular surface. 71,72 Overall, the most rigid residues of theses Hases are either located around the active sites (in particular the cysteines bound to the NiFe and proximal FeS clusters, which present remarkably small RMSF's in the all-atom simulation, see Figure SI3), or at the S/L interface, a common feature of multidomain proteic systems. 58,73−75 Next to the proximal cluster, DfHis228 L and AaHis237 L also present small rigidity peaks, and are thought to play a part in the O 2 -tolerance of the Hase from S. enterica.…”

Section: ■ Materials and Methodsmentioning

confidence: 98%

Multiscale Simulations Give Insight into the Hydrogen In and Out Pathways of [NiFe]-Hydrogenases from Aquifex aeolicus and Desulfovibrio fructosovorans

et al. 2014

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[NiFe]-hydrogenases catalyze the cleavage of molecular hydrogen into protons and electrons and represent promising tools for H2-based technologies such as biofuel cells. However, many aspects of these enzymes remain to be understood, in particular how the catalytic center can be protected from irreversible inactivation by O2. In this work, we combined homology modeling, all-atom molecular dynamics, and coarse-grain Brownian dynamics simulations to investigate and compare the dynamic and mechanical properties of two [NiFe]-hydrogenases: the soluble O2-sensitive enzyme from Desulfovibrio fructosovorans, and the O2-tolerant membrane-bound hydrogenase from Aquifex aeolicus. We investigated the diffusion pathways of H2 from the enzyme surface to the central [NiFe] active site, and the possible proton pathways that are used to evacuate hydrogen after the oxidation reaction. Our results highlight common features of the two enzymes, such as a Val/Leu/Arg triad of key residues that controls ligand migration and substrate access in the vicinity of the active site, or the key role played by a Glu residue for proton transfer after hydrogen oxidation. We show specificities of each hydrogenase regarding the enzymes internal tunnel network or the proton transport pathways.

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A QM/MM study of proton transport pathways in a [NiFe] hydrogenase

Cited by 60 publications

References 43 publications

Analyses of the Large Subunit Histidine-Rich Motif Expose an Alternative Proton Transfer Pathway in [NiFe] Hydrogenases

Analyses of the Large Subunit Histidine-Rich Motif Expose an Alternative Proton Transfer Pathway in [NiFe] Hydrogenases

Amino acid modified Ni catalyst exhibits reversible H ₂ oxidation/production over a broad pH range at elevated temperatures

Multiscale Simulations Give Insight into the Hydrogen In and Out Pathways of [NiFe]-Hydrogenases from Aquifex aeolicus and Desulfovibrio fructosovorans

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A QM/MM study of proton transport pathways in a [NiFe] hydrogenase

Cited by 60 publications

References 43 publications

Analyses of the Large Subunit Histidine-Rich Motif Expose an Alternative Proton Transfer Pathway in [NiFe] Hydrogenases

Analyses of the Large Subunit Histidine-Rich Motif Expose an Alternative Proton Transfer Pathway in [NiFe] Hydrogenases

Amino acid modified Ni catalyst exhibits reversible H 2 oxidation/production over a broad pH range at elevated temperatures

Multiscale Simulations Give Insight into the Hydrogen In and Out Pathways of [NiFe]-Hydrogenases from Aquifex aeolicus and Desulfovibrio fructosovorans

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Amino acid modified Ni catalyst exhibits reversible H ₂ oxidation/production over a broad pH range at elevated temperatures