Theoretical Insights into the Aerobic Hydrogenase Activity of Molybdenum–Copper CO Dehydrogenase

The Mo/Cu-dependent CO dehydrogenase from O. carboxydovorans is an enzyme that is able to catalyse CO oxidation to CO 2 ; moreover, it also expresses hydrogenase activity, as it is able to oxidize H 2 . Here, we have studied the dihydrogen oxidation catalysis by this enzyme using QM/MM calculations. Our results indicate that the equatorial oxo ligand of Mo is the best suited base for catalysis. Moreover, extraction of the first proton from H 2 by means of this basic centre leads to the formation of a Mo–OH–Cu I H hydride that allows for the stabilization of the copper hydride, otherwise known to be very unstable. In light of our results, two mechanisms for the hydrogenase activity of the enzyme are proposed. The first reactive channel depends on protonation of the sulphur atom of a Cu-bound cysteine residues, which appears to favour the binding and activation of the substrate. The second reactive channel involves a frustrated Lewis pair, formed by the equatorial oxo group bound to Mo and by the copper centre. In this case, no binding of the hydrogen molecule to the Cu center is observed but once H 2 enters into the active site, it can be split following a low-energy path.

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QM/MM study of the binding of H2 to MoCu CO dehydrogenase: development and applications of improved H2 van der Waals parameters

Journal of Molecular Modeling ◽

10.1007/s00894-020-04655-3 ◽

2021 ◽

Vol 27 (3) ◽

Author(s):

Anna Rovaletti ◽

Claudio Greco ◽

Ulf Ryde

Keyword(s):

Active Site ◽

Hydrogen Oxidation ◽

Van Der Waals ◽

Oxidation Mechanism ◽

Oxidation Catalysis ◽

Hydrogenase Activity ◽

Binding Modes ◽

Co Dehydrogenase ◽

Enzyme Active Site ◽

New Perspective

AbstractThe MoCu CO dehydrogenase enzyme not only transforms CO into CO2 but it can also oxidise H2. Even if its hydrogenase activity has been known for decades, a debate is ongoing on the most plausible mode for the binding of H2 to the enzyme active site and the hydrogen oxidation mechanism. In the present work, we provide a new perspective on the MoCu-CODH hydrogenase activity by improving the in silico description of the enzyme. Energy refinement—by means of the BigQM approach—was performed on the intermediates involved in the dihydrogen oxidation catalysis reported in our previously published work (Rovaletti, et al. “Theoretical Insights into the Aerobic Hydrogenase Activity of Molybdenum–Copper CO Dehydrogenase.” Inorganics 7 (2019) 135). A suboptimal description of the H2–HN(backbone) interaction was observed when the van der Waals parameters described in previous literature for H2 were employed. Therefore, a new set of van der Waals parameters is developed here in order to better describe the hydrogen–backbone interaction. They give rise to improved binding modes of H2 in the active site of MoCu CO dehydrogenase. Implications of the resulting outcomes for a better understanding of hydrogen oxidation catalysis mechanisms are proposed and discussed.

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Mechanism of selective benzene hydroxylation catalyzed by iron-containing zeolites

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1813849115 ◽

2018 ◽

Vol 115 (48) ◽

pp. 12124-12129 ◽

Cited By ~ 3

Author(s):

Benjamin E. R. Snyder ◽

Max L. Bols ◽

Hannah M. Rhoda ◽

Pieter Vanelderen ◽

Lars H. Böttger ◽

...

Keyword(s):

High Activity ◽

Active Site ◽

Active Sites ◽

High Performance ◽

Density Functional ◽

Catalyst Deactivation ◽

Density Functional Theory Calculations ◽

Oxidation Catalysis ◽

Spectroscopic Techniques ◽

Benzene Hydroxylation

A direct, catalytic conversion of benzene to phenol would have wide-reaching economic impacts. Fe zeolites exhibit a remarkable combination of high activity and selectivity in this conversion, leading to their past implementation at the pilot plant level. There were, however, issues related to catalyst deactivation for this process. Mechanistic insight could resolve these issues, and also provide a blueprint for achieving high performance in selective oxidation catalysis. Recently, we demonstrated that the active site of selective hydrocarbon oxidation in Fe zeolites, named α-O, is an unusually reactive Fe(IV)=O species. Here, we apply advanced spectroscopic techniques to determine that the reaction of this Fe(IV)=O intermediate with benzene in fact regenerates the reduced Fe(II) active site, enabling catalytic turnover. At the same time, a small fraction of Fe(III)-phenolate poisoned active sites form, defining a mechanism for catalyst deactivation. Density-functional theory calculations provide further insight into the experimentally defined mechanism. The extreme reactivity of α-O significantly tunes down (eliminates) the rate-limiting barrier for aromatic hydroxylation, leading to a diffusion-limited reaction coordinate. This favors hydroxylation of the rapidly diffusing benzene substrate over the slowly diffusing (but more reactive) oxygenated product, thereby enhancing selectivity. This defines a mechanism to simultaneously attain high activity (conversion) and selectivity, enabling the efficient oxidative upgrading of inert hydrocarbon substrates.

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CO temperature-programmed desorption of a hexameric copper hydride nanocluster catalyst supported on functionalized MWCNTs for active site characterization in a low-temperature water–gas shift reaction

Chemical Engineering Journal ◽

10.1016/j.cej.2018.10.215 ◽

2019 ◽

Vol 377 ◽

pp. 120278 ◽

Cited By ~ 5

Author(s):

Luqmanulhakim Baharudin ◽

Alex C.K. Yip ◽

Vladimir B. Golovko ◽

Matthew I.J. Polson ◽

Matthew J. Watson

Keyword(s):

Active Site ◽

Temperature Programmed Desorption ◽

Water Gas Shift ◽

Copper Hydride ◽

Water Gas Shift Reaction ◽

Temperature Programmed ◽

Shift Reaction ◽

Water Gas ◽

Functionalized Mwcnts ◽

Temperature Water

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Nickel(II) in an almost regular tetrahedral thiolate environment: a first generation synthetic analogue of the active site of nickel CO-dehydrogenase

Journal of the Chemical Society Dalton Transactions ◽

10.1039/b102607k ◽

2001 ◽

pp. 1387-1388 ◽

Cited By ~ 12

Author(s):

Matt C. Smith ◽

Steven Longhurst ◽

J. Elaine Barclay ◽

Stephen P. Cramer ◽

Sian C. Davies ◽

...

Keyword(s):

Active Site ◽

First Generation ◽

Synthetic Analogue ◽

Co Dehydrogenase

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Synthetic Analogues of the Active Site of the A-Cluster of Acetyl Coenzyme A Synthase/CO Dehydrogenase: Syntheses, Structures, and Reactions with CO

Inorganic Chemistry ◽

10.1021/ic0520465 ◽

2006 ◽

Vol 45 (8) ◽

pp. 3424-3436 ◽

Cited By ~ 41

Author(s):

Todd C. Harrop ◽

Marilyn M. Olmstead ◽

Pradip K. Mascharak

Keyword(s):

Active Site ◽

Coenzyme A ◽

Co Dehydrogenase ◽

Synthetic Analogues ◽

Acetyl Coenzyme A ◽

Acetyl Coenzyme ◽

Acetyl Coenzyme A Synthase

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Evidence for an essential serine residue in the active site of the Theta class glutathione transferases

Biochemical Journal ◽

10.1042/bj3110247 ◽

1995 ◽

Vol 311 (1) ◽

pp. 247-250 ◽

Cited By ~ 96

Author(s):

P G Board ◽

M Coggan ◽

M C J Wilce ◽

M W Parker

Keyword(s):

Crystal Structure ◽

Active Site ◽

Catalytic Mechanism ◽

Glutathione Transferases ◽

Tyrosine Residue ◽

Serine Residue ◽

Sulphur Atom ◽

N Terminus ◽

Australian Sheep ◽

Consistent Feature

A consistent feature of the Alpha-, Mu- and Pi-class glutathione transferases (GSTs) is the presence near the N-terminus of a tyrosine residue that contributes to the activation of glutathione. While this residue appears to be conserved in many Theta-class GSTs, its absence in some suggested that the Theta-class GSTs may have a significantly different structure or catalytic mechanism. The elucidation of the crystal structure of the Theta-class GST from the Australian sheep blowfly, Lucilia cuprina, has indicated that a serine residue rather than a tyrosine residue can form a hydrogen bond with the glutathionyl sulphur atom. The present studies show that mutation of Ser-9 to alanine substantially inactivates the L. cuprina GST, confirming its importance in the reaction mechanism. As this serine is conserved in all Theta-class enzymes reported so far, it seems that an active-site serine is a significant factor that distinguishes the Theta-class GSTs from members of the Alpha-, Mu- and Pi-class isoenzymes.

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Nickel(II) complexes bound to an [Fe4S4] cluster via bridging thiolates:synthesis and crystal structure of model compounds for the active site of nickel CO dehydrogenase

Chemical Communications ◽

10.1039/cc9960000777 ◽

1996 ◽

pp. 777 ◽

Cited By ~ 15

Author(s):

Frank Osterloh ◽

Wolfgang Saak ◽

Detlev Haase ◽

Siegfried Pohl

Keyword(s):

Crystal Structure ◽

Active Site ◽

Co Dehydrogenase ◽

Model Compounds

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Converting the NiFeS Carbon Monoxide Dehydrogenase to a Hydrogenase and a Hydroxylamine Reductase

Journal of Bacteriology ◽

10.1128/jb.184.21.5894-5897.2002 ◽

2002 ◽

Vol 184 (21) ◽

pp. 5894-5897 ◽

Cited By ~ 17

Author(s):

Jongyun Heo ◽

Marcus T. Wolfe ◽

Christopher R. Staples ◽

Paul W. Ludden

Keyword(s):

Carbon Monoxide ◽

Amino Acid ◽

Active Site ◽

Reductase Activity ◽

Carbon Monoxide Dehydrogenase ◽

Hydrogenase Activity ◽

Uptake Hydrogenase ◽

Site Cluster ◽

Metal Ligand

ABSTRACT Substitution of one amino acid for another at the active site of an enzyme usually diminishes or eliminates the activity of the enzyme. In some cases, however, the specificity of the enzyme is changed. In this study, we report that the changing of a metal ligand at the active site of the NiFeS-containing carbon monoxide dehydrogenase (CODH) converts the enzyme to a hydrogenase or a hydroxylamine reductase. CODH with alanine substituted for Cys531 exhibits substantial uptake hydrogenase activity, and this activity is enhanced by treatment with CO. CODH with valine substituted for His265 exhibits hydroxylamine reductase activity. Both Cys531 and His265 are ligands to the active-site cluster of CODH. Further, CODH with Fe substituted for Ni at the active site acquires hydroxylamine reductase activity.

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