A theoretical study of the cis-dihydroxylation mechanism in naphthalene 1,2-dioxygenase

Bassan, Arianna; Blomberg, Margareta R. A.; Siegbahn, Per E. M.

doi:10.1007/s00775-004-0537-0

Cited by 110 publications

(140 citation statements)

References 49 publications

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“…12A). 52 However, as argued below, this is not the case for a high-spin Fe(IV)=O species. An analysis of the natural orbitals and natural spin orbitals calculated for SOSP1 (see Fig.…”

Section: Formation Of the Epoxide Intermediate Direct Formation Of Epmentioning

confidence: 96%

Role of Substrate Positioning in the Catalytic Reaction of 4-Hydroxyphenylpyruvate Dioxygenase—A QM/MM Study

et al. 2014

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Ring hydroxylation and coupled rearrangement reactions catalyzed by 4-hydroxyphenylpyruvate dioxygenase were studied with the QM/MM method ONIOM(B3LYP:AMBER). For electrophilic attack of the ferryl species on the aromatic ring, five channels were considered: attacks on the three ring atoms closest to the oxo ligand (C1, C2, C6) and insertion of oxygen across two bonds formed by them (C1-C2, C1-C6). For the subsequent migration of the carboxymethyl substituent, two possible directions were tested (C1→C2, C1→C6) and two different mechanisms were sought (step-wise radical, single-step heterolytic). In addition, formation of an epoxide (side)product and benzylic hydroxylation, as catalyzed by the closely related hydroxymandelate synthase, were investigated. From the computed reaction free energy profiles it follows that the most likely mechanism of 4-hydroxyphenylpyruvate dioxygenase involves electrophilic attack on the C1 carbon of the ring and subsequent singlestep heterolytic migration of the substituent. Computed values of the kinetic isotope effect for this step are inverse, consistent with available experimental data. Electronic structure arguments for the preferred mechanism of attack on the ring are also presented.

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“…12A). 52 However, as argued below, this is not the case for a high-spin Fe(IV)=O species. An analysis of the natural orbitals and natural spin orbitals calculated for SOSP1 (see Fig.…”

Section: Formation Of the Epoxide Intermediate Direct Formation Of Epmentioning

confidence: 96%

Role of Substrate Positioning in the Catalytic Reaction of 4-Hydroxyphenylpyruvate Dioxygenase—A QM/MM Study

et al. 2014

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“…The incorporation of the oxygen requires the activation by iron (63,64). Activated oxygen species or iron peroxo or hydroperoxo intermediates (28,65) at the non-heme catalytic site can attack nitrogen and following concerted oxygen transfer from the high valent iron-oxo species suggested in cytochrome P-450 (63,66), phthalate dioxygenase (63), putidamonoxin (63), naphthalene dioxygenase (28), and methane monooxygenase (64,67) to the nitrogen may produce aromatic nitro-metabolite pyrrolnitrin.…”

Section: Discussionmentioning

confidence: 99%

Reconstitution and Characterization of Aminopyrrolnitrin Oxygenase, a Rieske N-Oxygenase That Catalyzes Unusual Arylamine Oxidation

Lee

Simurdiak

Zhao

2005

Journal of Biological Chemistry

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O suggested that the oxygen atoms in the pyrrolnitrin product are derived exclusively from molecular oxygen. In addition, it was found that the oxygenation of the arylamine substrates catalyzed by PrnD occurs at the enzyme active site and does not involve free radical chain reactions. By analogy to known examples of arylamine oxidation, a catalytic mechanism for the bioconversion of amino pyrrolnitrin into pyrrolnitrin was proposed. Our results should facilitate further mechanistic and crystallographic studies of this arylamine oxygenase and may provide a new enzymatic route for the synthesis of aromatic nitro compounds from their corresponding aromatic amines.

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“…Computational studies favor the former for enzyme reactions, but show that the latter is a possible reactive species in small molecule model compounds where the low spin state of the metal can be accessed 48,49 . The crystal structure of the side-on bound hydroperoxo complex of NDO has been solved after exposing the substrate-bound crystal of NDO to O 2 as shown in Fig.…”

Section: Rieske Cis-diol Forming Dioxygenasesmentioning

confidence: 99%

“…Both mechanistic scenarios have received support from computational studies 48,49 . One direct approach to resolving this controversy has been to show that hydrogen peroxide added to the substrate complex of naphthalene or benzoate dioxygenase (BZDO) in the resting state with the Rieske cluster oxidized and the mononuclear iron reduced yields nearly stoichiometric amounts of product (a peroxide shunt) 50,51 .…”

Section: Rieske Cis-diol Forming Dioxygenasesmentioning

confidence: 99%

“…It was suggested that after achieving the formal Fe(V)=O state, the mononuclear iron accepts another electron from a Rieske cluster located in a remote subunit of the multimeric enzyme. Thus, the true reactive species would be either an Fe(II)-(hydro)peroxo or an Fe(IV)-oxo-hydroxo, which would presumably be more readily stabilized in a biological system.Both mechanistic scenarios have received support from computational studies 48,49 . One direct approach to resolving this controversy has been to show that hydrogen peroxide added to the substrate complex of naphthalene or benzoate dioxygenase (BZDO) in the resting state with the Rieske cluster oxidized and the mononuclear iron reduced yields nearly stoichiometric amounts of product (a peroxide shunt) 50,51 .…”

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Versatility of biological non-heme Fe(II) centers in oxygen activation reactions

2008

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Oxidase and oxygenase enzymes allow the use of relatively unreactive O 2 in biochemical reactions. Many of the mechanistic strategies employed in nature for this key reaction are represented within the 2-His-1-carboxylate facial triad family of non-heme Fe(II) containing enzymes. The open face of the metal coordination sphere opposite the three endogenous ligands participates directly in the reaction chemistry. Here, data from several studies are presented showing that reductive O 2 activation within this family is initiated by substrate (and in some cases co-substrate or cofactor) binding, which then allows coordination of O 2 to the metal. From this starting point, both the O 2 activation process and the reactions with substrates diverge broadly. The reactive species formed in these reactions have been proposed to encompass four oxidation states of iron and all forms of reduced O 2 as well as several of the reactive oxygen species that derive from O-O bond cleavage.Dioxygen serves at least three quite different roles that profoundly impact aerobic life. The most commonly appreciated role is to serve as the terminal electron acceptor in processes such as oxidative phosphorylation that yield the central energy-rich molecules used throughout metabolism. The second, no less important role is to serve as the source for many of the oxygen atoms found in the essential molecules of biological systems such as steroid hormones, aromatic amino acids, neurotransmitters, signalling molecules, and regulatory factors 1 . Also, processes operating on a global scale, such as the recovery of the enormous quantities of carbon sequestered as lignin in plant life or the oxidation of the billions of tons of methane generated by anaerobes before it can enter the atmosphere, also involve oxygen incorporation from O 2 2 ,3 . On a more local scale, biodegradation of both aliphatic and aromatic toxic compounds often begins with the incorporation of oxygen 4 . The third, and least appreciated role played by dioxygen in aerobic organisms involves neither energy conversion nor oxygen incorporation. Rather, some enzymes can convert dioxygen to alternative forms that are, in effect, highly specialized reagents that are used to catalyze the synthesis of important biomolecules. An excellent example of the latter role for O 2 is the biosynthesis of penicillintype antibiotics 5,6 , which is discussed in more detail later in this review.Dioxygen is an attractive reagent for use in a biological system because its high potential reactivity is held in check by its molecular structure. The triplet ground state of O 2 that results from the presence of two unpaired electrons in degenerate molecular orbitals makes the direct reaction with singlet molecules, the spin-paired state of most potential reaction partners, a forbidden process 7 . The central question that has faced chemists and biochemists for the half Competing Interests StatementThe authors declare no competing financial interests. Of course, the answers to this question are of fundam...

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A theoretical study of the cis-dihydroxylation mechanism in naphthalene 1,2-dioxygenase

Cited by 110 publications

References 49 publications

Role of Substrate Positioning in the Catalytic Reaction of 4-Hydroxyphenylpyruvate Dioxygenase—A QM/MM Study

Role of Substrate Positioning in the Catalytic Reaction of 4-Hydroxyphenylpyruvate Dioxygenase—A QM/MM Study

Reconstitution and Characterization of Aminopyrrolnitrin Oxygenase, a Rieske N-Oxygenase That Catalyzes Unusual Arylamine Oxidation

Versatility of biological non-heme Fe(II) centers in oxygen activation reactions

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