Key Structural Motifs Balance Metal Binding and Oxidative Reactivity in a Heterobimetallic Mn/Fe Protein

Kisgeropoulos, Effie C.; Griese, Julia J.; Smith, Zachary; Branca, Rui M.; Schneider, Camille R.; Högbom, Martin; Shafaat, Hannah S.

doi:10.1021/jacs.0c00333

Cited by 28 publications

(43 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To circumvent this limitation, enzymes typically use transition metals, mostly iron, to catalyze reactions with O 2 [6–15] . Transition metals also contain unpaired electrons so may react with O 2 via a spin‐allowed reaction.…”

Section: Introductionmentioning

confidence: 99%

DpgC‐Catalyzed Peroxidation of 3,5‐Dihydroxyphenylacetyl‐CoA (DPA‐CoA): Insights into the Spin‐Forbidden Transition and Charge Transfer Mechanisms**

Ortega

Zanchet

Sanz-Sanz

et al. 2020

Chemistry A European J

View full text Add to dashboard Cite

Despite being a very strong oxidizing agent, most organic molecules are not oxidized in the presence of O2 at room temperature because O2 is a diradical whereas most organic molecules are closed‐shell. Oxidation then requires a change in the spin state of the system, which is forbidden according to non‐relativistic quantum theory. To overcome this limitation, oxygenases usually rely on metal or redox cofactors to catalyze the incorporation of, at least, one oxygen atom into an organic substrate. However, some oxygenases do not require any cofactor, and the detailed mechanism followed by these enzymes remains elusive. To fill this gap, here the mechanism for the enzymatic cofactor‐independent oxidation of 3,5‐dihydroxyphenylacetyl‐CoA (DPA‐CoA) is studied by combining multireference calculations on a model system with QM/MM calculations. Our results reveal that intersystem crossing takes place without requiring the previous protonation of molecular oxygen. The characterization of the electronic states reveals that electron transfer is concomitant with the triplet–singlet transition. The enzyme plays a passive role in promoting the intersystem crossing, although spontaneous reorganization of the water wire connecting the active site with the bulk presets the substrate for subsequent chemical transformations. The results show that the stabilization of the singlet radical‐pair between dioxygen and enolate is enough to promote spin‐forbidden reaction without the need for neither metal cofactors nor basic residues in the active site.

show abstract

Section: Introductionmentioning

confidence: 99%

DpgC‐Catalyzed Peroxidation of 3,5‐Dihydroxyphenylacetyl‐CoA (DPA‐CoA): Insights into the Spin‐Forbidden Transition and Charge Transfer Mechanisms**

Ortega

Zanchet

Sanz-Sanz

et al. 2020

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…To circumvent this limitation, enzymes typically use transition metals, mostly iron, to catalyze reactions with O 2 . [6][7][8][9][10][11][12][13][14][15] Transition metals also contain unpaired electrons so may react with O 2 via a spin-allowed reaction. Moreover, metals can be used to preactivate the substrate, forming a radical that can react with O 2 .…”

Section: Introductionmentioning

confidence: 99%

DpgC-Catalyzed Peroxidation of DPA-CoA: Insights onto the Spin-Forbidden Transition and Charge Transfer Mechanisms

Ortega¹,

Zanchet²,

Sanz-Sanz³

et al. 2020

Preprint

View full text Add to dashboard Cite

Oxygenases are a family of enzymes that catalyse the breaking of molecular oxygen with incorporation of, at least, one oxygen atom into an organic substrate. Since molecular oxygen is a diradical and most organic molecules have no unpaired-electrons, reactions catalysed by oxygenases involve changes in the spin state of the system that are forbidden in non-relativistic quantum theory. To overcome this limitation, oxygenases usually require metal or redox cofactors for catalysis. Intriguingly, some oxygenases can catalyse oxygen incorporation reactions even in the absence of any cofactor, but the detailed mechanism followed by these enzymes to overcome this limitation is still unknown. In the present work we give insight onto the mechanism for the enzymatic cofactor-independent oxidation of 3,5-dihydroxyphenylacetyl-CoA (DPA-CoA) by the combination of multi-reference calculations on a model system, with QM/MM calculations for the enzymatic reaction. Our results reveal that intersystem crossing takes place without requiring concerted protonation of molecular oxygen. We characterized and identifed the nine concurrent electronic states, showing that a first electron transfer is concomitant with the triplet-singlet transition (intersystem crossing). The enzyme apparently plays a passive role in promoting the intersystem crossing, although spontaneous reorganization of the water-wire connecting the active site with the bulk presets the substrate for subsequent chemical transformations. We believe that our results are fairly general showing that stabilization of the singlet radical-pair state between molecular oxygen and enolates is enough to promote spin-forbidden reaction without the need of neither metal cofactors nor basic residues in the active site.

show abstract

“…Wasserstoffbrückenbindungen sind also auch beim Binden der Metalle wichtig und könnten helfen, neue heterobimetallische Proteine zu synthetisieren. 48) Die Covid-19-Pandemie hat auch anorganische Chemiker dazu gebracht, sich mit dem Virus zu befassen. Deshalb gab es mehrere Beispiele für Koordinationsverbindungen mit Aktivität gegen Sars-CoV-2 oder den Eisen-Schwefel-Cluster in Sars-CoV-2.…”

Section: Bioanorganische Chemieunclassified

Trendbericht Anorganik 2022 Teil 2: Nebengruppen und Koordinationschemie, Bioanorganik und mehr

Ringenberg¹,

Werncke²

2022

Nachr Chem

View full text Add to dashboard Cite

show abstract

Key Structural Motifs Balance Metal Binding and Oxidative Reactivity in a Heterobimetallic Mn/Fe Protein

Abstract: Access to the published version may require subscription. N.B. When citing this work, cite the original published paper.

Cited by 28 publications

References 78 publications

DpgC‐Catalyzed Peroxidation of 3,5‐Dihydroxyphenylacetyl‐CoA (DPA‐CoA): Insights into the Spin‐Forbidden Transition and Charge Transfer Mechanisms**

DpgC‐Catalyzed Peroxidation of 3,5‐Dihydroxyphenylacetyl‐CoA (DPA‐CoA): Insights into the Spin‐Forbidden Transition and Charge Transfer Mechanisms**

DpgC-Catalyzed Peroxidation of DPA-CoA: Insights onto the Spin-Forbidden Transition and Charge Transfer Mechanisms

Trendbericht Anorganik 2022 Teil 2: Nebengruppen und Koordinationschemie, Bioanorganik und mehr

Contact Info

Product

Resources

About