Oxygen activation in extradiol catecholate dioxygenases – a density functional study

Christian, Gemma J.; Ye, Shengfa; Neese, Frank

doi:10.1039/c2sc00754a

Cited by 69 publications

(153 citation statements)

References 49 publications

Supporting

Mentioning

125

Contrasting

Unclassified

Order By: Relevance

“…For example, differences in active site structures correlate with divergent regiospecificity and mechanisms in the intradiol and extradiol catechol oxygenases ( Figure 24) Figure 24 Proposed mechanisms for the intradiol (left) and extradiol (right) dioxygenases (adapted from [145] and [168], respectively). Similar adducts also are proposed for other members of the family of enzymes that feature the supporting 2-His-1-carboxylate facial triad as a common structural motif.…”

Section: Dioxygen Activation By Non-heme Iron Complexesmentioning

confidence: 97%

Transition Metal Complexes and the Activation of Dioxygen

Yee

Tolman

2014

Metal Ions in Life Sciences

View full text Add to dashboard Cite

In order to address how diverse metalloprotein active sites, in particular those containing iron and copper, guide O₂binding and activation processes to perform diverse functions, studies of synthetic models of the active sites have been performed. These studies have led to deep, fundamental chemical insights into how O₂coordinates to mono- and multinuclear Fe and Cu centers and is reduced to superoxo, peroxo, hydroperoxo, and, after O-O bond scission, oxo species relevant to proposed intermediates in catalysis. Recent advances in understanding the various factors that influence the course of O₂activation by Fe and Cu complexes are surveyed, with an emphasis on evaluating the structure, bonding, and reactivity of intermediates involved. The discussion is guided by an overarching mechanistic paradigm, with differences in detail due to the involvement of disparate metal ions, nuclearities, geometries, and supporting ligands providing a rich tapestry of reaction pathways by which O₂is activated at Fe and Cu sites.

show abstract

Section: Dioxygen Activation By Non-heme Iron Complexesmentioning

confidence: 97%

Transition Metal Complexes and the Activation of Dioxygen

Yee

Tolman

2014

Metal Ions in Life Sciences

View full text Add to dashboard Cite

show abstract

“…In more recent work, Neese and coworkers used a larger cluster model consisting of residues from the primary coordination sphere (H155, H214, and E267) and those in the second sphere (H200, N157, Y257, R243, and H248) that were found by crystallography to have interactions with the substrate, O 2 or the E267 ligand [54]. With this model, an earlier intermediate involving only the iron(II) center and O 2 could be found.…”

Section: Insights From Dft Calculationsmentioning

confidence: 99%

A two-electron-shell game: intermediates of the extradiol-cleaving catechol dioxygenases

2014

View full text Add to dashboard Cite

Extradiol catechol ring-cleaving dioxygenases function by binding both the organic substrate and O2 at a divalent metal center in the active site. They have proven to be a particularly versatile group of enzymes with which to study the O2 activation process. Here, recent studies of homoprotocatechuate 2,3-dioxygenase (HPCD) are summarized with the objective of showing how Nature can utilize the enzyme structure and the properties of the metal and the substrate to select among many possible chemical paths to achieve both specificity and efficiency. Possible intermediates in the mechanism have been trapped by swapping active site metals, introducing active site amino acid substituted variants, and using substrates with different electron donating capacities. While each of these intermediates could form part of a viable reaction pathway, kinetic measurements significantly limit the likely candidates. Structural, kinetic, spectroscopic and computational analysis of the various intermediates shed light on how catalytic efficiency can be achieved.

show abstract

“…In the absence of metal ions, the oxidation of 1,2-dihydroxy-3-keto-5-(methylthio)pentene yields the same products as ARD′ via a base-catalyzed oxidative cleavage, indicating that dioxygen activation is not needed for enzymatic activity. 6 Other studies have shown that non-heme iron proteins, in particular non-heme iron dioxygenases, require metal activation of dioxygen, 8,9 whereas in the presence of dioxygen alone, both ARD and ARD′ do not bind oxygen, further proving the requirement of sequential binding of the substrate followed by dioxygen binding for catalysis. 6 The exact mechanisms of the two reactions remain unknown.…”

Section: +mentioning

confidence: 99%

Metal-Dependent Activity of Fe and Ni Acireductone Dioxygenases: How Two Electrons Reroute the Catalytic Pathway

Sparta

Valdez

Alexandrova

2013

Journal of Molecular Biology

View full text Add to dashboard Cite

Two virtually identical acireductone dioxygenases, ARD and ARD′, catalyze completely different oxidation reactions of the same substrate, 1,2-dihydroxy-3-keto-5-(methylthio)pentene, depending exclusively on the nature of the bound metal. Fe 2+ -dependent ARD′ produces the α-keto acid precursor of methionine and formate and allows for the recycling of methionine in cells. Ni 2+ -dependent ARD instead produces methylthiopropionate, CO, and formate, and exits the methionine salvage cycle. This mechanistic difference has not been understood to date but has been speculated to be due to the difference in coordination of the substrate to Fe 2+ versus Ni 2+ : forming a five-membered ring versus a six-membered ring, respectively, thus exposing different carbon atoms for the attack by O 2 . Here, using mixed quantum-classical molecular dynamics simulations followed by the density functional theory mechanistic investigation, we show that, contrary to the old hypothesis, both metals preferentially bind the substrate as a six-membered ring, exposing the exact same sites to the attack by O 2 . It is the electronic properties of the metals that are then responsible for the system following different reaction paths, to yield the respective products. We fully explain the puzzling metal-induced difference in functionality between ARD and ARD′ and, in particular, propose a new mechanism for ARD′. All results are in agreement with available isotopic substitution and other experimental data.

show abstract

Oxygen activation in extradiol catecholate dioxygenases – a density functional study

Cited by 69 publications

References 49 publications

Transition Metal Complexes and the Activation of Dioxygen

Transition Metal Complexes and the Activation of Dioxygen

A two-electron-shell game: intermediates of the extradiol-cleaving catechol dioxygenases

Metal-Dependent Activity of Fe and Ni Acireductone Dioxygenases: How Two Electrons Reroute the Catalytic Pathway

Contact Info

Product

Resources

About