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Annette Rompel - One of the best experts on this subject based on the ideXlab platform.

  • similar but still different which amino acid residues are responsible for varying activities in type iii Copper Enzymes
    ChemBioChem, 2021
    Co-Authors: Ioannis Kampatsikas, Annette Rompel
    Abstract:

    Type-III Copper Enzymes like polyphenol oxidases (PPOs) are ubiquitous among organisms and play a significant role in the formation of pigments. PPOs comprise different enzyme groups, including tyrosinases (TYRs) and catechol oxidases (COs). TYRs catalyze the o-hydroxylation of monophenols and the oxidation of o-diphenols to the corresponding o-quinones (EC 1.14.18.1). In contrast, COs only catalyze the oxidation of o-diphenols to the corresponding o-quinones (EC 1.10.3.1). To date (August 2020), 102 PDB entries encompassing 18 different proteins from 16 organisms and several mutants have been reported, identifying key residues for tyrosinase activity. The structural similarity between TYRs and COs, especially within and around the active center, complicates the elucidation of their modes of action on a structural basis. However, mutagenesis studies illuminate residues that influence the two activities and show that crystallography on its own cannot elucidate the enzymatic activity mode. Several amino acid residues around the diCopper active center have been proposed to play an essential role in the two different activities. Herein, we critically review the role of all residues identified so far that putatively affect the two activities of PPOs.

  • identification of amino acid residues responsible for c h activation in type iii Copper Enzymes by generating tyrosinase activity in a catechol oxidase
    Angewandte Chemie, 2020
    Co-Authors: Ioannis Kampatsikas, Matthias Pretzler, Annette Rompel
    Abstract:

    Tyrosinases (TYRs) catalyze the hydroxylation of phenols and the oxidation of the resulting o -diphenols to o -quinones, while catechol oxidases (COs) exhibit only the latter activity. Aurone synthase (AUS) is not able to react with classical tyrosinase substrates like tyramine and L -tyrosine, while it can hydroxylate its natural substrate isoliquiritigenin. The structural difference of TYRs, COs and AUS at the base of their divergent catalytic activities is still a puzzle. Therefore, a library of 39 mutants of AUS from Coreopsis grandiflora ( Cg AUS) was generated and the activity studies proved that the reactivity of the three conserved histidines (HisA 2 , HisB 1 and HisB 2 ) is tuned by their adjacent residues (HisB 1 +1, HisB 2 +1 and waterkeeper residue) either to react as stronger bases or / and to stabilize a position permissive for substrate proton shuffling. In the newly proposed monophenolase reaction cycle the deprotonation of the incoming monophenolic substrate en route to the active oxy- site is supported by one of the three conserved histidines HisA 2 , HisB 1 and HisB 2 , initiating the C-H activation in TYRs in contrast to COs. In particular, we present mutants with a TYR activity of the same order of magnitude as found in natural plant TYRs, which is a strong indication that the molecular basis of TYR against CO activity has been revealed. This provides the understanding for C-H activation based on the type-III Copper center to be used in future biotechnological processes.

  • what causes the different functionality in type iii Copper Enzymes a state of the art perspective
    Inorganica Chimica Acta, 2017
    Co-Authors: Matthias Pretzler, Annette Rompel
    Abstract:

    Abstract The structural difference between tyrosinase and catechol oxidase as the basis for their catalytic activity is still a puzzle although several crystal structures of both Enzymes exist. In this review we discuss the structural motifs that had been proposed to be responsible for the lack of hydroxylase activity. However, up to now, all worked out structural restrictions could be disproved by more recent crystal structures of type-III-Copper Enzymes. The search for the function-determining amino acids continues and after decades of intensive research we still do not know more than that the substrate binding residues must be directly responsible for the mono- and/or diphenolase activity. In the last part the review discusses possibilities to address the topic in the future: What causes the different functionality in type-III-Copper Enzymes?

  • the structure of a plant tyrosinase from walnut leaves reveals the importance of substrate guiding residues for enzymatic specificity
    Angewandte Chemie, 2015
    Co-Authors: Aleksandar Bijelic, Christian Molitor, Matthias Pretzler, Florime Zekiri, Annette Rompel
    Abstract:

    Tyrosinases and catechol oxidases are members of the class of type III Copper Enzymes. While tyrosinases accept both mono- and o-diphenols as substrates, only the latter substrate is converted by catechol oxidases. Researchers have been working for decades to elucidate the monophenolase/diphenolase specificity on a structural level and have introduced an early hypothesis that states that the reason for the lack of monophenolase activity in catechol oxidases may be its structurally restricted active site. However, recent structural and biochemical studies of this enzyme class have raised doubts about this theory. Herein, the first crystal structure of a plant tyrosinase (from Juglans regia) is presented. The structure reveals that the distinction between mono- and diphenolase activity does not depend on the degree of restriction of the active site, and thus a more important role for amino acid residues located at the entrance to and in the second shell of the active site is proposed.

  • type 3 Copper proteins recent advances on polyphenol oxidases
    Advances in Protein Chemistry, 2014
    Co-Authors: Cornelia Kaintz, Stephan Gerhard Mauracher, Annette Rompel
    Abstract:

    Abstract Recent investigations in the study of plant, fungal, and bacterial type-3 Copper proteins are reviewed. Focus is given to three Enzymes: catechol oxidases (CO), tyrosinases, and aureusidin synthase. CO were mostly found in plants, however, in 2010 the first fungal CO was published. The first plant-originated tyrosinase was published in 2014, before tyrosinases were only reported in fungi, bacteria, and human. Aureusidin synthase from yellow snapdragon ( Antirrhinum majus ) was first published in 2000, as part of yellow flower coloration pathway. In the last years, many important results on type-3 Copper Enzymes originated from X-ray crystallographic investigations. In addition, studies on site-directed mutagenesis of amino acids around the active site were performed to identify the regions determining monophenolase and/or diphenolase activity. Although X-ray crystallographic structures of CO and tyrosinases are available, many questions like the response for the activation via proteases, sequence-based or structural-based differences between CO, as well as the physiological roles of many polyphenol oxidases still remain to be addressed.

Aurelien De La Lande - One of the best experts on this subject based on the ideXlab platform.

Matthias Pretzler - One of the best experts on this subject based on the ideXlab platform.

  • identification of amino acid residues responsible for c h activation in type iii Copper Enzymes by generating tyrosinase activity in a catechol oxidase
    Angewandte Chemie, 2020
    Co-Authors: Ioannis Kampatsikas, Matthias Pretzler, Annette Rompel
    Abstract:

    Tyrosinases (TYRs) catalyze the hydroxylation of phenols and the oxidation of the resulting o -diphenols to o -quinones, while catechol oxidases (COs) exhibit only the latter activity. Aurone synthase (AUS) is not able to react with classical tyrosinase substrates like tyramine and L -tyrosine, while it can hydroxylate its natural substrate isoliquiritigenin. The structural difference of TYRs, COs and AUS at the base of their divergent catalytic activities is still a puzzle. Therefore, a library of 39 mutants of AUS from Coreopsis grandiflora ( Cg AUS) was generated and the activity studies proved that the reactivity of the three conserved histidines (HisA 2 , HisB 1 and HisB 2 ) is tuned by their adjacent residues (HisB 1 +1, HisB 2 +1 and waterkeeper residue) either to react as stronger bases or / and to stabilize a position permissive for substrate proton shuffling. In the newly proposed monophenolase reaction cycle the deprotonation of the incoming monophenolic substrate en route to the active oxy- site is supported by one of the three conserved histidines HisA 2 , HisB 1 and HisB 2 , initiating the C-H activation in TYRs in contrast to COs. In particular, we present mutants with a TYR activity of the same order of magnitude as found in natural plant TYRs, which is a strong indication that the molecular basis of TYR against CO activity has been revealed. This provides the understanding for C-H activation based on the type-III Copper center to be used in future biotechnological processes.

  • what causes the different functionality in type iii Copper Enzymes a state of the art perspective
    Inorganica Chimica Acta, 2017
    Co-Authors: Matthias Pretzler, Annette Rompel
    Abstract:

    Abstract The structural difference between tyrosinase and catechol oxidase as the basis for their catalytic activity is still a puzzle although several crystal structures of both Enzymes exist. In this review we discuss the structural motifs that had been proposed to be responsible for the lack of hydroxylase activity. However, up to now, all worked out structural restrictions could be disproved by more recent crystal structures of type-III-Copper Enzymes. The search for the function-determining amino acids continues and after decades of intensive research we still do not know more than that the substrate binding residues must be directly responsible for the mono- and/or diphenolase activity. In the last part the review discusses possibilities to address the topic in the future: What causes the different functionality in type-III-Copper Enzymes?

  • the structure of a plant tyrosinase from walnut leaves reveals the importance of substrate guiding residues for enzymatic specificity
    Angewandte Chemie, 2015
    Co-Authors: Aleksandar Bijelic, Christian Molitor, Matthias Pretzler, Florime Zekiri, Annette Rompel
    Abstract:

    Tyrosinases and catechol oxidases are members of the class of type III Copper Enzymes. While tyrosinases accept both mono- and o-diphenols as substrates, only the latter substrate is converted by catechol oxidases. Researchers have been working for decades to elucidate the monophenolase/diphenolase specificity on a structural level and have introduced an early hypothesis that states that the reason for the lack of monophenolase activity in catechol oxidases may be its structurally restricted active site. However, recent structural and biochemical studies of this enzyme class have raised doubts about this theory. Herein, the first crystal structure of a plant tyrosinase (from Juglans regia) is presented. The structure reveals that the distinction between mono- and diphenolase activity does not depend on the degree of restriction of the active site, and thus a more important role for amino acid residues located at the entrance to and in the second shell of the active site is proposed.

Olivier Parisel - One of the best experts on this subject based on the ideXlab platform.

Francis K Yoshimoto - One of the best experts on this subject based on the ideXlab platform.

  • formation and cleavage of c c bonds by enzymatic oxidation reduction reactions
    Chemical Reviews, 2018
    Co-Authors: Peter F Guengerich, Francis K Yoshimoto
    Abstract:

    Many oxidation–reduction (redox) Enzymes, particularly oxygenases, have roles in reactions that make and break C–C bonds. The list includes cytochrome P450 and other heme-based monooxygenases, heme-based dioxygenases, nonheme iron mono- and dioxygenases, flavoproteins, radical S-adenosylmethionine Enzymes, Copper Enzymes, and peroxidases. Reactions involve steroids, intermediary metabolism, secondary natural products, drugs, and industrial and agricultural chemicals. Many C–C bonds are formed via either (i) coupling of diradicals or (ii) generation of unstable products that rearrange. C–C cleavage reactions involve several themes: (i) rearrangement of unstable oxidized products produced by the Enzymes, (ii) oxidation and collapse of radicals or cations via rearrangement, (iii) oxygenation to yield products that are readily hydrolyzed by other Enzymes, and (iv) activation of O2 in systems in which the binding of a substrate facilitates O2 activation. Many of the Enzymes involve metals, but of these, iron i...