Type-3 Copper Proteins

Kaintz, Cornelia; Mauracher, S.G.; Rompel, Annette

doi:10.1016/bs.apcsb.2014.07.001

Cited by 50 publications

(22 citation statements)

References 83 publications

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“…Tyrosinases (EC 1.14.18.1) are widespread polyphenol oxidases of bacteria, fungi, plants, and animals (Zaidi et al, 2014) that participate of critical biological functions, such as photoprotection (mammals), immune system and wound-healing processes (plants, fungi, and insects), and in spore and sexual organs maturation (fungi) (Agarwal et al, 2019). These metalloenzymes carry a characteristic type-3 copper center formed of two copper ions (CuA and CuB), each one connected to three conserved histidine residues (Goldfeder et al, 2014), which catalyzes hydroxylation monophenols to diphenols (monophenolase reaction) and oxidation diphenols to quinones (diphenolase reaction), using molecular oxygen as electron acceptor in both reactions (Kaintz et al, 2014). This process occurs as a catalytic cycle, where the active site shifts from active oxy (Cu II -O2 -Cu II ) state to intermediate met (Cu II -OH -Cu II ) state, and then, to a resting deoxy (Cu I -Cu I ) state that requires a new dioxygen for reactivation (Ba and Vinoth Kumar, 2017).…”

Section: Introductionmentioning

confidence: 99%

New tyrosinases with a broad spectrum of action against contaminants of emerging concern: Insights fromin silicoanalyses

Senra

Fonseca

2020

Preprint

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Tyrosinases (EC 1.14.18.1) are type-3 copper metalloenzymes with strong oxidative capacities and low allosteric selectivity to phenolic and non-phenolic aromatic compounds that have been used as biosensors and biocatalysts to mitigate the impacts of environmental contaminants over aquatic ecosystems. However, the widespread use of these polyphenol oxidases is limited by elevated production costs and restricted knowledge on their spectrum of action. Here, six tyrosinase homologs were identified and characterized from the genomes of 4 widespread freshwater ciliates using bioinformatics. Binding energies between 3D models of these homologs and ~1000 contaminants of emerging concern (CECs), including fine chemicals, pharmaceuticals, personal care products, illicit drugs, natural toxins, and pesticides were estimated through virtual screening, suggesting their spectrum of action and potential uses in environmental biotechnology might be considerably broader than previously thought. Moreover, considering that many ciliates, including those caring tyrosinase genes within their genomes are fast-growing unicellular microeukaryotes that can be efficiently culturable at large-scales under in vitro conditions, should be regarded as potential low-cost sources for the production of relevant biotechnological molecules.

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Section: Introductionmentioning

confidence: 99%

New tyrosinases with a broad spectrum of action against contaminants of emerging concern: Insights fromin silicoanalyses

Senra

Fonseca

2020

Preprint

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“…TYRs, COs and AUS are summarized under the umbrella term polyphenol oxidases (PPOs). These enzymes are widely distributed in bacteria, fungi, plants and animals (Mayer, 2006;Tran et al, 2012;Kaintz, Mauracher et al, 2014;Pretzler et al, 2015). Tyrosinases are able to catalyze the ortho-hydroxylation of monophenols to o-diphenols (monophenolase activity; EC 1.14.18.1) coupled with the subsequent two-electron oxidation of o-diphenols to the corresponding o-quinones (diphenolase activity; EC 1.10.3.1) (Mason, 1955;Mayer et al, 1966).…”

Section: Introductionmentioning

confidence: 99%

In crystalloactivity tests with latent apple tyrosinase and two mutants reveal the importance of the mutated sites for polyphenol oxidase activity

et al. 2017

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Tyrosinases are type 3 copper enzymes that belong to the polyphenol oxidase (PPO) family and are able to catalyze both the ortho-hydroxylation of monophenols and their subsequent oxidation to o-quinones, which are precursors for the biosynthesis of colouring substances such as melanin. The first plant pro-tyrosinase from Malus domestica (MdPPO1) was recombinantly expressed in its latent form (56.4 kDa) and mutated at four positions around the catalytic pocket which are believed to influence the activity of the enzyme. Mutating the amino acids, which are known as activity controllers, yielded the mutants MdPPO1-Ala239Thr and MdPPO1-Leu243Arg, whereas mutation of the so-called water-keeper and gatekeeper residues resulted in the mutants MdPPO1-Glu234Ala and MdPPO1-Phe259Ala, respectively. The wild-type enzyme and two of the mutants, MdPPO1-Ala239Thr and MdPPO1-Phe259Ala, were successfully crystallized, leading to single crystals that diffracted to 1.35, 1.55 and 1.70 Å resolution, respectively. All crystals belonged to space group P2 1 2 1 2 1 , exhibiting similar unit-cell parameters: a = 50.70, b = 80.15, c = 115.96 Å for the wild type, a = 50.58, b = 79.90, c = 115.76 Å for MdPPO1-Ala239Thr and a = 50.53, b = 79.76, c = 116.07 Å for MdPPO1-Phe259Ala. In crystallo activity tests with the crystals of the wild type and the two mutants were performed by adding the monophenolic substrate tyramine and the diphenolic substrate dopamine to crystal-containing drops. The effects of the mutation on the activity of the enzyme were observed by colour changes of the crystals owing to the conversion of the substrates to dark chromophore products.

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“…Tyrosinases (TYRs,E C1.14.18.1 and EC 1.10.3.1) and catechol oxidases (COs,E C1.10.3.1) are type III coppercontaining metalloenzymes that constitute the class of polyphenol oxidases (PPOs). [1,2] PPOs are present in archaea, bacteria, fungi, plants,and animals. [3][4][5][6] To date,plant, fungal, and bacterial PPOs have been reported to exist in both their pro-(or latent) and active form in vivo.…”

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confidence: 99%

A Peptide‐Induced Self‐Cleavage Reaction Initiates the Activation of Tyrosinase

et al. 2019

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The conversion of inactive pro‐polyphenol oxidases (pro‐PPOs) into the active enzyme results from the proteolytic cleavage of its C‐terminal domain. Herein, a peptide‐mediated cleavage process that activates pro‐ Md PPO1 ( Malus domestica ) is reported. Mass spectrometry, mutagenesis studies, and X‐ray crystal‐structure analysis of pro‐ Md PPO1 (1.35 Å) and two separated C‐terminal domains, one obtained upon self‐cleavage of pro‐ Md PPO1 and the other one produced independently, were applied to study the observed self‐cleavage. The sequence Lys 355–Val 370 located in the linker between the active and the C‐terminal domain is indispensable for the self‐cleavage. Partial introduction (Lys 352–Ala 360) of this peptide into the sequence of two other PPOs, Md PPO2 and aurone synthase ( Cg AUS1), triggered self‐cleavage in the resulting mutants. This is the first experimental proof of a self‐cleavage‐inducing peptide in PPOs, unveiling a new mode of activation for this enzyme class that is independent of any external protease.

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Type-3 Copper Proteins

Cited by 50 publications

References 83 publications

New tyrosinases with a broad spectrum of action against contaminants of emerging concern: Insights fromin silicoanalyses

New tyrosinases with a broad spectrum of action against contaminants of emerging concern: Insights fromin silicoanalyses

In crystalloactivity tests with latent apple tyrosinase and two mutants reveal the importance of the mutated sites for polyphenol oxidase activity

A Peptide‐Induced Self‐Cleavage Reaction Initiates the Activation of Tyrosinase

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