Investigations on the Role of Proton-Coupled Electron Transfer in Hydrogen Activation by [FeFe]-Hydrogenase

Mulder, David W.; Ratzloff, Michael W.; Bruschi, Maurizio; Greco, Claudio; Koonce, Evangeline; Peters, John W.; King, Paul W.

doi:10.1021/ja508629m

Cited by 111 publications

(245 citation statements)

References 74 publications

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“…The intramolecular ET step led to binding and activation of H 2 at the open coordination site of the Fe d II site, similar to the mechanism based on enzyme studies as proposed in Fig. 6, Scheme B [166].…”

Section: The Emerging Role Of [4fe-4s] In the [Fefe]-hydrogenase Catasupporting

confidence: 69%

[FeFe]- and [NiFe]-hydrogenase diversity, mechanism, and maturation

Peters

Schut

Boyd

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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410

397

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The [FeFe]- and [NiFe]-hydrogenases catalyze the formal interconversion between hydrogen and protons and electrons, possess characteristic non-protein ligands at their catalytic sites and thus share common mechanistic features. Despite the similarities between these two types of hydrogenases, they clearly have distinct evolutionary origins and likely emerged from different selective pressures. [FeFe]-hydrogenases are widely distributed in fermentative anaerobic microorganisms and likely evolved under selective pressure to couple hydrogen production to the recycling of electron carriers that accumulate during anaerobic metabolism. In contrast, many [NiFe]-hydrogenases catalyze hydrogen oxidation as part of energy metabolism and were likely key enzymes in early life and arguably represent the predecessors of modern respiratory metabolism. Although the reversible combination of protons and electrons to generate hydrogen gas is the simplest of chemical reactions, the [FeFe]- and [NiFe]-hydrogenases have distinct mechanisms and differ in the fundamental chemistry associated with proton transfer and control of electron flow that also help to define catalytic bias. A unifying feature of these enzymes is that hydrogen activation itself has been restricted to one solution involving diatomic ligands (carbon monoxide and cyanide) bound to an Fe ion. On the other hand, and quite remarkably, the biosynthetic mechanisms to produce these ligands are exclusive to each type of enzyme. Furthermore, these mechanisms represent two independent solutions to the formation of complex bioinorganic active sites for catalyzing the simplest of chemical reactions, reversible hydrogen oxidation. As such, the [FeFe]- and [NiFe]-hydrogenases are arguably the most profound case of convergent evolution. This article is part of a Special Issue entitled: Fe/S proteins: Analysis, structure, function, biogenesis and diseases.

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Section: The Emerging Role Of [4fe-4s] In the [Fefe]-hydrogenase Catasupporting

confidence: 69%

[FeFe]- and [NiFe]-hydrogenase diversity, mechanism, and maturation

Peters

Schut

Boyd

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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410

397

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“…This geometry was earlier calculated to be stabilized by ∼8 kJ/mol (48). It has been suggested that H 2 may form a similar H-bond to adt during the catalytic reaction (37,49,51,53). Substrate (H 2 ) or inhibitor (CO) binding at the active site thus may be governed by intramolecular rather than protein-cofactor interactions.…”

Section: Discussionmentioning

confidence: 83%

“…13 CO editing of the H-cluster has been achieved using 13 C-precursors during H-cluster assembly or exposure of [FeFe]-hydrogenases to 13 CO gas (18,(24)(25)(26)33 CO groups also facilitates analysis of structure-function relationships using quantum chemical calculations. However, relatively few computational studies to calculate vibrational modes of the diatomic ligands have been carried out (35)(36)(37)(38)(39).We compared three different [FeFe]-hydrogenase proteins, HYDA1, from the green alga Chlamydomonas reinhardtii, and the bacterial enzymes CPI from Clostridium pasteurianum and DDH from Desulfovibrio desulfuricans. HYDA1 represents the "minimal unit" of biological hydrogen turnover as it exclusively binds the H-cluster, whereas CPI and DDH hold accessory iron-sulfur clusters (3,40).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

“…Introduction of 13 CO groups also facilitates analysis of structure-function relationships using quantum chemical calculations. However, relatively few computational studies to calculate vibrational modes of the diatomic ligands have been carried out (35)(36)(37)(38)(39).…”

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confidence: 99%

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Stepwise isotope editing of [FeFe]-hydrogenases exposes cofactor dynamics

Senger

Mebs

Duan

et al. 2016

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

137

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The six-iron cofactor of [FeFe]-hydrogenases (H-cluster) is the most efficient H 2 -forming catalyst in nature. It comprises a diiron active site with three carbon monoxide (CO) and two cyanide (CN − ) ligands in the active oxidized state (H ox ) and one additional CO ligand in the inhibited state (H ox -CO). The diatomic ligands are sensitive reporter groups for structural changes of the cofactor. Their vibrational dynamics were monitored by real-time attenuated total reflection Fouriertransform infrared spectroscopy. Combination of 13 CO gas exposure, blue or red light irradiation, and controlled hydration of three different [FeFe]-hydrogenase proteins produced 8 H ox and 16 H ox -CO species with all possible isotopic exchange patterns. Extensive density functional theory calculations revealed the vibrational mode couplings of the carbonyl ligands and uniquely assigned each infrared spectrum to a specific labeling pattern. For H ox -CO, agreement between experimental and calculated infrared frequencies improved by up to one order of magnitude for an apical CN − at the distal iron ion of the cofactor as opposed to an apical CO. For H ox , two equally probable isomers with partially rotated ligands were suggested. Interconversion between these structures implies dynamic ligand reorientation at the H-cluster. Our experimental protocol for site-selective 13 CO isotope editing combined with computational species assignment opens new perspectives for characterization of functional intermediates in the catalytic cycle.[FeFe]-hydrogenase | isotope editing | infrared spectroscopy | density functional theory | cofactor dynamics T he reduction of protons to form molecular hydrogen (H 2 ) is catalyzed by [FeFe]-hydrogenases (1, 2). With a turnover rate of up to 10,000 H 2 molecules per second in a thermodynamically reversible reaction (3-5), [FeFe]-hydrogenases inspired synthetic hydrogen catalysts (6-8) and renewable fuel technology applications (9, 10). The mechanism of catalysis at the active site cofactor (H-cluster) needs to be elucidated. Further information on functional intermediates is required (11-16) and expected to emerge from spectroscopic studies on H-cluster constructs carrying siteselective isotopic reporter groups (17)(18)(19)(20) Formation of H ox -CO does not affect the formal redox state of the H-cluster, but leads to increased spin delocalization over the diiron site (28). CO binding inhibits H 2 turnover and protects the enzyme against O 2 and light-induced degradation (24,29,30).The vibrational modes of the CO and CN − ligands at the diiron site are well accessible by infrared (IR) spectroscopy because they are separated from protein backbone and liquid water bands.Infrared spectroscopy therefore has pioneered elucidation of the molecular structure of the H-cluster and identification of several redox states (24, 31). In particular, the CO stretching frequencies are highly sensitive to structural isomerism, redox transitions, ligand binding, and isotope exchange (11,12,15,18,24,31,32). 13 CO editing ...

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Catalytic Bias in Enzymatic Metal Cofactor‐Based Oxidation–Reduction Catalysis

Varghese¹,

Mulder²,

Raugei³

et al. 2021

Encyclopedia of Inorganic and Bioinorganic Chemistry

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Catalytic bias refers to the relative rate preference of a catalyst for either the forward or reverse direction. In enzymatic metal cofactor‐based oxidation–reduction catalysis, the tuning of catalytic bias plays an underlying role in controlling rates of reactivity. For this, enzymes have evolved complex active sites that can exist in multiple oxidation states with differing reduction potentials in order to achieve challenging multi‐step, oxidation–reduction reactions. Conceivably, the relative stability of the intermediates that contribute to determining the rate‐limiting step of the catalytic cycle could impose catalytic bias, although mechanisms for this concept are just beginning to be realized. As one example, recent work on Clostridium pasteurianum [FeFe]‐hydrogenases which catalyze reversible hydrogen oxidation have shown that the differential stabilization/destabilization of active site oxidation states through either static or dynamic protein interactions can preferentially promote either the hydrogen oxidation or proton reduction direction of the reaction. This revealed how an enzymatic cofactor can impose bias in oxidation–reduction catalysis through various tuning mechanisms by protein scaffold interactions. The hypothesis based on achieving catalytic bias through the modulation of cofactor oxidation states critical for the reaction cycle can be extended more generally to other cofactor‐based oxidation–reductions catalysts. The current understanding of catalytic bias has significant implications for the design of synthetic catalysts used in industrial settings, as well as providing a greater fundamental understanding of the factors that control metabolic processes in all life.

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Investigations on the Role of Proton-Coupled Electron Transfer in Hydrogen Activation by [FeFe]-Hydrogenase

Cited by 111 publications

References 74 publications

[FeFe]- and [NiFe]-hydrogenase diversity, mechanism, and maturation

[FeFe]- and [NiFe]-hydrogenase diversity, mechanism, and maturation

Stepwise isotope editing of [FeFe]-hydrogenases exposes cofactor dynamics

Catalytic Bias in Enzymatic Metal Cofactor‐Based Oxidation–Reduction Catalysis

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