Tyrosinase versus Catecholoxidase: ein Asparagin macht den Unterschied

Solem, Even; Tuczek, Felix; Decker, Heinz

doi:10.1002/ange.201508534

Cited by 24 publications

(3 citation statements)

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“…The first X‐ray crystallographic characterization of a tyrosinase from the bacterium Streptomyces castaneoglobisporus was presented by Matoba et al . In the meantime, many more crystal structures of copper‐containing polyphenol oxidases (PPOs) have appeared, allowing to relate their structural differences to the functional discrimination between TY and CO activity ,. Nevertheless, details of the molecular mechanism of tyrosinase are still unclear or under discussion ,…”

Section: Methodsmentioning

confidence: 99%

“…[6][7]8] Nevertheless, details of the molecular mechanism of tyrosinase are still unclear or under discussion. [6][7]8] Important information regarding the reactivity of tyrosinase may be obtained from small-molecule model systems. Many research groups followed this line of research; correspondingly, the number of functional models of tyrosinase has steadily increased over the years (Scheme 1).…”

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Click. Coordinate. Catalyze. Using CuAAC Click Ligands in Small‐Molecule Model Chemistry of Tyrosinase

et al. 2018

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Three triazolylmethylpyridine ligands are synthesized using the copper‐catalyzed azide‐alkyne cycloaddition (CuAAC). The corresponding copper(I) complexes are investigated as catalysts for the oxygenation of several monophenols, in analogy to the enzyme tyrosinase. Importantly, they show a higher catalytic activity than previously investigated systems. This is ascribed to the lower charge donation of the electron‐poor triazole heterocycle, supporting the hydroxylation of phenolic substrates by an electrophilic substitution mechanism.

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Section: Methodsmentioning

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Click. Coordinate. Catalyze. Using CuAAC Click Ligands in Small‐Molecule Model Chemistry of Tyrosinase

et al. 2018

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“…Along with a glutamate, the Asn residue activates conserved water towards deprotonation of monophenols. If Asn is missing, only diphenolase activity is observed [9].…”

Section: Introductionmentioning

confidence: 98%

Tyrosinase and catechol oxidase activity of copper(I) complexes supported by imidazole-based ligands: structure–reactivity correlations

2016

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Four new imidazole-based ligands, 4-((1H-imidazol-4-yl)methyl)-2-phenyl-4,5-dihydrooxyzole (L OL 1), 4-((1H-imidazol-4-yl)methyl)-2-(tert-butyl)-4,5-dihydrooxyzole (L OL 2), 4-((1H-imidazol-4-yl)methyl)-2-methyl-4,5-dihydrooxyzole (L OL 3), and N-(2,2-dimethylpropylidene)-2-(1-trityl-1H-imidazol-4-yl-)ethyl amine (L imz 1), have been synthesized. The corresponding copper(I) complexes [Cu(I)(L OL 1)(CH3CN)]PF6 (CuL OL 1), [Cu(I)(L OL 2)(CH3CN)]PF6 (CuL OL 2), [Cu(I)(L OL 3)(CH3CN)]PF6 (CuL OL 3), [Cu(I)(L imz 1)(CH3CN)2]PF6 (CuL imz 1) as well as the Cu(I) complex derived from the known ligand bis(1-methylimidazol-2-yl)methane (BIMZ), [Cu(I)(BIMZ)(CH3CN)]PF6 (CuBIMZ), are screened as catalysts for the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC-H2) to 3,5-di-tert-butylquinone (3,5-DTBQ). The primary reaction product of these oxidations is 3,5-di-tert-butylsemiquinone (3,5-DTBSQ) which slowly converts to 3,5-DTBQ. Saturation kinetic studies reveal a trend of catalytic activity in the order CuL OL 3 ≈ CuL OL 1 > CuBIMZ > CuL OL 2 > CuL imz 1. Additionally, the catalytic activity of the copper(I) complexes towards the oxygenation of monophenols is investigated. As substrates 2,4-di-tert-butylphenol (2,4-DTBP-H), 3-tert-butylphenol (3-TBP-H), 4-methoxyphenol (4-MeOP-H), N-acetyl-L-tyrosine ethyl ester monohydrate (NATEE) and 8-hydroxyquinoline are employed. The oxygenation products are identified and characterized with the help of UV/Vis and NMR spectroscopy, mass spectrometry, and fluorescence measurements. Whereas the copper complexes with ligands containing combinations of imidazole and imine functions or two imidazole units (CuL imz 1 and CuBIMZ) are found to exhibit catalytic tyrosinase activity, the systems with ligands containing oxazoline just mediate a stoichiometric conversion. Correlations between the structures of the complexes and their reactivities are discussed.

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Simplest Monodentate Imidazole Stabilization of the oxy‐Tyrosinase Cu₂O₂ Core: Phenolate Hydroxylation through a Cu^III Intermediate

et al. 2016

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Tyrosinases (Ty) are ubiquitous binuclear copper enzymes that oxygenate to Cu(II) 2 O 2 ( S P) cores bonded by three histidine Nτ-imidazoles per Cu center. Synthetic monodentate imidazole bonded S P species self-assemble in a near quantitative manner at −125°C, but Nπ-ligation has been required. Herein, we disclose the syntheses and reactivity of three Nτ-imidazole bonded S P species at solution temperatures of −145°C, which was achieved using a eutectic mixture of THF and 2-MeTHF. The addition of anionic phenolates affords a Cu(III) 2 O 2 (O) species, where the bonded phenolates hydroxylate to catecholates in high yields. Similar O intermediates are not observed using Nπ-bonded S P species, hinting that Nτ-imidazole ligation, conserved in all characterized Ty, has functional advantage beyond active-site flexibility. Substrate accessibility to the oxygenated Cu 2 O 2 core and stabilization of a high oxidation state of the copper centers are suggested from these minimalistic models. Graphical AbstractCorrespondence to: T. Daniel P. Stack. Tyrosinases (Ty) are ubiquitous binuclear Cu enzymes responsible for melanin biosynthesis via regioselective tyrosine aromatic hydroxylation to form catechols, and its subsequent oxidation to quinones. Spectroscopic and X-ray crystallographic analysis of its oxygenated form (oxyTy) reveals a side-on μ-η 2 :η 2 peroxide dicopper (II) ( S P) species ligated exclusively by six histidine residues through the τ-nitrogen (Nτ) of each imidazole ( Figure 1). [1] This results in a highly accessible S P Cu 2 O 2 core where the 4-substituent of the imidazoles are positioned remotely. This Nτ-ligated S P core is conserved in oxygenated hemocyanin (oxyHc) proteins [2] , an evolutionary descendant of Ty [3] responsible for reversible dioxygen (O 2 ) uptake and storage. [1b, 4] The reactivity difference between oxyTy and oxyHc is attributed to substrate access to the oxygenated Cu 2 O 2 core, [5] as partially denatured hemocyanin proteins can exhibit mono-oxygenase reactivity. [6] Alternatively, more sterically-demanding and less-flexible π-nitrogen (Nπ) imidazole ligation is observed exclusively in electron-transfer blue-copper sites, suggesting Nτ-ligation may serve a functional purpose such as providing flexibility for the O 2 capture, allowing substrate access to the oxygenated S P core, and potentially stabilizing higher oxidation states of copper in the mono-oxygenase reaction. [1c, 7] Synthetic S P analogues of oxyTy have received extensive attention over the last few decades. [4a, 8] Stoichiometric phenolate oxidation to catecholates is possible at the low reaction temperatures required to stabilize most synthetic S P species, although several catalytic systems operating at elevated temperatures are now known. [9] These complexes are generally supported by multi-nucleating alkyl amines or heterocycles such as pyridines, pyrazoles or benzimidazoles. However, synthetic S P species exclusively ligated by imidazoles, especially by imidazoles bearing an N-H group [10] , are...

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Tyrosinase versus Catecholoxidase: ein Asparagin macht den Unterschied

Cited by 24 publications

References 41 publications

Click. Coordinate. Catalyze. Using CuAAC Click Ligands in Small‐Molecule Model Chemistry of Tyrosinase

Click. Coordinate. Catalyze. Using CuAAC Click Ligands in Small‐Molecule Model Chemistry of Tyrosinase

Tyrosinase and catechol oxidase activity of copper(I) complexes supported by imidazole-based ligands: structure–reactivity correlations

Simplest Monodentate Imidazole Stabilization of the oxy‐Tyrosinase Cu₂O₂ Core: Phenolate Hydroxylation through a Cu^III Intermediate

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Tyrosinase versus Catecholoxidase: ein Asparagin macht den Unterschied

Cited by 24 publications

References 41 publications

Click. Coordinate. Catalyze. Using CuAAC Click Ligands in Small‐Molecule Model Chemistry of Tyrosinase

Click. Coordinate. Catalyze. Using CuAAC Click Ligands in Small‐Molecule Model Chemistry of Tyrosinase

Tyrosinase and catechol oxidase activity of copper(I) complexes supported by imidazole-based ligands: structure–reactivity correlations

Simplest Monodentate Imidazole Stabilization of the oxy‐Tyrosinase Cu2O2 Core: Phenolate Hydroxylation through a CuIII Intermediate

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Simplest Monodentate Imidazole Stabilization of the oxy‐Tyrosinase Cu₂O₂ Core: Phenolate Hydroxylation through a Cu^III Intermediate