Origin of the Proton-transfer Step in the Cofactor-free (1H)-3-Hydroxy-4-oxoquinaldine 2,4-Dioxygenase

Hernández-Ortega, Aitor; Quesne, Matthew G.; Bui, Soi; Heuts, Dominic P. H. M.; Steiner, Roberto A.; Heyes, Derren J.; Visser, Sam P. de; Scrutton, Nigel S.

doi:10.1074/jbc.m113.543033

Cited by 34 publications

(50 citation statements)

References 53 publications

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“…Analysis of the three-dimensional structure of Hod and the biochemical data of His251Ala Hodmuteins showed that His251 is the catalytically active base that accepts a proton from the substrate. The formed substrate anion then reacts with molecular oxygen without the need for a metal or a cofactor (29)(30)(31). Hod was partially inhibited by imidazole (as Lcp) in a concentration-dependent manner.…”

Section: Discussionmentioning

confidence: 95%

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Rubber Oxygenase and Latex Clearing Protein Cleave Rubber to Different Products and Use Different Cleavage Mechanisms

Birke

Jendrossek

2014

Appl Environ Microbiol

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. RoxA was able to cleave isolated Lcp-derived oligo-isoprenoid molecules to ODTD. Inhibitor studies, spectroscopic investigations and metal analysis gave no indication for the presence of iron, other metals, or cofactors in Lcp. Our results suggest that Lcp could be a member of the growing group of cofactor-independent oxygenases and differs in the cleavage mechanism from heme-dependent RoxA. In conclusion, RoxA and Lcp represent two different answers to the same biochemical problem, the cleavage of polyisoprene, a polymer that has carbon-carbon double bonds as the only functional groups for enzymatic attack.

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Section: Discussionmentioning

confidence: 95%

“…Hod was partially inhibited by imidazole (as Lcp) in a concentration-dependent manner. However, the mechanism of inhibition remained unknown (29). Interestingly, Lcp proteins of different species have two conserved His residues (His198 and His203 in Lcp of Streptomyces sp.…”

Section: Discussionmentioning

confidence: 99%

Rubber Oxygenase and Latex Clearing Protein Cleave Rubber to Different Products and Use Different Cleavage Mechanisms

Birke

Jendrossek

2014

Appl Environ Microbiol

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“…To keep the computations tractable most of the surrounding aminoacids were excised, and only the Asp-His dyad responsible for the initial deprotonation of substrate (Steiner et al, 2010; Hernandez-Ortega et al, 2014) and charge stabilization of the 3 I 1 / 1 I 1 intermediates was kept. Table 1 shows that this truncation has very modest effects on the reaction energetics, and should therefore not introduce relevant errors.…”

Section: Resultsmentioning

confidence: 99%

“…As in previous work by Hernandez-Ortega et al (2014), all computations were repeated for four different (1 H )-3-hydroxy-4-oxoquinolines to ascertain the influence of different substituents (methyl, pentyl, fluor and nitro) in the reaction course. The minimum-energy crossing points found (Fig.…”

Section: Resultsmentioning

confidence: 99%

Refining the reaction mechanism of O₂towards its co-substrate in cofactor-free dioxygenases

Silva

2016

PeerJ

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Cofactor-less oxygenases perform challenging catalytic reactions between singlet cosubstrates and triplet oxygen, in spite of apparently violating the spin-conservation rule. In 1-H -3-hydroxy-4-oxoquinaldine-2,4-dioxygenase, the active site has been suggested by quantum chemical computations to fine tune triplet oxygen reactivity, allowing it to interact rapidly with its singlet substrate without the need for spin inversion, and in urate oxidase the reaction is thought to proceed through electron transfer from the deprotonated substrate to an aminoacid sidechain, which then feeds the electron to the oxygen molecule. In this work, we perform additional quantum chemical computations on these two systems to elucidate several intriguing features unaddressed by previous workers. These computations establish that in both enzymes the reaction proceeds through direct electron transfer from co-substrate to O 2 followed by radical recombination, instead of minimum-energy crossing points between singlet and triplet potential energy surfaces without formal electron transfer. The active site does not affect the reactivity of oxygen directly but is crucial for the generation of the deprotonated form of the co-substrates, which have redox potentials far below those of their protonated forms and therefore may transfer electrons to oxygen without sizeable thermodynamic barriers. This mechanism seems to be shared by most cofactor-less oxidases studied so far.Subjects Biochemistry

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“…For instance, the enzyme 1-H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase performs an intradiol-type dioxygenation of an aromatic substrate in the absence of co-factor although the reaction is slow. 15,16 Therefore, co-factors, such as transition metals in metalloenzymes, are expected to speed up biochemical reactions significantly by lowering the rate determining energy barrier in a reaction mechanism. Metalloenzymes can be mononuclear or binuclear or contain more than two metal centers, 17 however, in this review we will focus on mononuclear iron complexes only.…”

Section: Introductionmentioning

confidence: 99%

The Role of Nonheme Transition Metal-Oxo, -Peroxo, and -Superoxo Intermediates in Enzyme Catalysis and Reactions of Bioinspired Complexes

Faponle

Visser

2017

Inorganic Reaction Mechanisms

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Transition metals are common co-factors in enzymes and enable catalysis to take place via reaction barriers that are accessible at room temperature. Oxygen activating metalloenzymes are versatile species in Nature involved in vital processes ranging from biodegradation to biosynthesis. Since oxygen activating intermediates are not readily amenable to experimental study, research has started to focus on biomimetic model systems that have the active site coordination sphere and structural features, but react in solution. In our research group, we have been involved in computational modeling of heme and nonheme iron dioxygenases as well as biomimetic models of these complexes. In this contribution an overview is given on recent results of the characterization and reactivity patterns of metaloxo, metal-peroxo and metal-superoxo complexes. In particular, in recent studies attempts were made to trap and characterize the short-lived oxygen bound intermediate in the catalytic cycle of cysteine dioxygenase. Many suggested structures could be ruled out by theoretical considerations, yet these also provided suggestions of possible candidates for the experimentally observed spectra. In addition, we review recent studies on the nonheme iron(III)-hydroperoxo species and how its reactivity patterns with arenes are dramatically different from those found for heme iron(III)-hydroperoxo species. The final two projects show a series of computational studies on manganese(V)-oxo and side-on manganese(III)-peroxo moieties that identify a unique spin state reactivity pattern with a surprising product distribution.3

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Origin of the Proton-transfer Step in the Cofactor-free (1H)-3-Hydroxy-4-oxoquinaldine 2,4-Dioxygenase

Cited by 34 publications

References 53 publications

Rubber Oxygenase and Latex Clearing Protein Cleave Rubber to Different Products and Use Different Cleavage Mechanisms

Rubber Oxygenase and Latex Clearing Protein Cleave Rubber to Different Products and Use Different Cleavage Mechanisms

Refining the reaction mechanism of O₂towards its co-substrate in cofactor-free dioxygenases

The Role of Nonheme Transition Metal-Oxo, -Peroxo, and -Superoxo Intermediates in Enzyme Catalysis and Reactions of Bioinspired Complexes

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Origin of the Proton-transfer Step in the Cofactor-free (1H)-3-Hydroxy-4-oxoquinaldine 2,4-Dioxygenase

Cited by 34 publications

References 53 publications

Rubber Oxygenase and Latex Clearing Protein Cleave Rubber to Different Products and Use Different Cleavage Mechanisms

Rubber Oxygenase and Latex Clearing Protein Cleave Rubber to Different Products and Use Different Cleavage Mechanisms

Refining the reaction mechanism of O2towards its co-substrate in cofactor-free dioxygenases

The Role of Nonheme Transition Metal-Oxo, -Peroxo, and -Superoxo Intermediates in Enzyme Catalysis and Reactions of Bioinspired Complexes

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Refining the reaction mechanism of O₂towards its co-substrate in cofactor-free dioxygenases