Tyrosinase

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Qiuyu Gong - One of the best experts on this subject based on the ideXlab platform.

  • detection of misdistribution of Tyrosinase from melanosomes to lysosomes and its upregulation under psoralen ultraviolet a with a melanosome targeting Tyrosinase fluorescent probe
    Analytical Chemistry, 2016
    Co-Authors: Jin Zhou, Wen Shi, Qiuyu Gong
    Abstract:

    Tyrosinase is regarded as an important biomarker of melanoma cancer, and its metabolism is closely related to some severe skin diseases such as vitiligo. Since Tyrosinase is mainly located in the melanosomes of melanocytes, a probe that can specifically detect and image tysosinase in melanosomes would be in urgent demand to study the behavior of the enzyme in cells, but unfortunately, no melanosome-targeting Tyrosinase fluorescent probe has been reported so far to the best of our knowledge. In this work, we have developed such a new probe, Mela-TYR, which bears morpholine as a melanosome-targeting group and 4-aminophenol as a Tyrosinase reaction group. The probe exhibits not only a highly sensitive and selective off-on response to Tyrosinase via oxidization cleavage, but also an accurate targeting ability toward the acidic organelles of melanosomes and lyososomes, which is validated by colocalization experiments with mCherry-tagged melanosomes as well as DND-99 (a commercial dye). The probe has been used ...

  • Detection of Misdistribution of Tyrosinase from Melanosomes to Lysosomes and Its Upregulation under Psoralen/Ultraviolet A with a Melanosome-Targeting Tyrosinase Fluorescent Probe.
    Analytical chemistry, 2016
    Co-Authors: Jin Zhou, Wen Shi, Qiuyu Gong
    Abstract:

    Tyrosinase is regarded as an important biomarker of melanoma cancer, and its metabolism is closely related to some severe skin diseases such as vitiligo. Since Tyrosinase is mainly located in the melanosomes of melanocytes, a probe that can specifically detect and image tysosinase in melanosomes would be in urgent demand to study the behavior of the enzyme in cells, but unfortunately, no melanosome-targeting Tyrosinase fluorescent probe has been reported so far to the best of our knowledge. In this work, we have developed such a new probe, Mela-TYR, which bears morpholine as a melanosome-targeting group and 4-aminophenol as a Tyrosinase reaction group. The probe exhibits not only a highly sensitive and selective off-on response to Tyrosinase via oxidization cleavage, but also an accurate targeting ability toward the acidic organelles of melanosomes and lyososomes, which is validated by colocalization experiments with mCherry-tagged melanosomes as well as DND-99 (a commercial dye). The probe has been used ...

Jin Zhou - One of the best experts on this subject based on the ideXlab platform.

  • detection of misdistribution of Tyrosinase from melanosomes to lysosomes and its upregulation under psoralen ultraviolet a with a melanosome targeting Tyrosinase fluorescent probe
    Analytical Chemistry, 2016
    Co-Authors: Jin Zhou, Wen Shi, Qiuyu Gong
    Abstract:

    Tyrosinase is regarded as an important biomarker of melanoma cancer, and its metabolism is closely related to some severe skin diseases such as vitiligo. Since Tyrosinase is mainly located in the melanosomes of melanocytes, a probe that can specifically detect and image tysosinase in melanosomes would be in urgent demand to study the behavior of the enzyme in cells, but unfortunately, no melanosome-targeting Tyrosinase fluorescent probe has been reported so far to the best of our knowledge. In this work, we have developed such a new probe, Mela-TYR, which bears morpholine as a melanosome-targeting group and 4-aminophenol as a Tyrosinase reaction group. The probe exhibits not only a highly sensitive and selective off-on response to Tyrosinase via oxidization cleavage, but also an accurate targeting ability toward the acidic organelles of melanosomes and lyososomes, which is validated by colocalization experiments with mCherry-tagged melanosomes as well as DND-99 (a commercial dye). The probe has been used ...

  • Detection of Misdistribution of Tyrosinase from Melanosomes to Lysosomes and Its Upregulation under Psoralen/Ultraviolet A with a Melanosome-Targeting Tyrosinase Fluorescent Probe.
    Analytical chemistry, 2016
    Co-Authors: Jin Zhou, Wen Shi, Qiuyu Gong
    Abstract:

    Tyrosinase is regarded as an important biomarker of melanoma cancer, and its metabolism is closely related to some severe skin diseases such as vitiligo. Since Tyrosinase is mainly located in the melanosomes of melanocytes, a probe that can specifically detect and image tysosinase in melanosomes would be in urgent demand to study the behavior of the enzyme in cells, but unfortunately, no melanosome-targeting Tyrosinase fluorescent probe has been reported so far to the best of our knowledge. In this work, we have developed such a new probe, Mela-TYR, which bears morpholine as a melanosome-targeting group and 4-aminophenol as a Tyrosinase reaction group. The probe exhibits not only a highly sensitive and selective off-on response to Tyrosinase via oxidization cleavage, but also an accurate targeting ability toward the acidic organelles of melanosomes and lyososomes, which is validated by colocalization experiments with mCherry-tagged melanosomes as well as DND-99 (a commercial dye). The probe has been used ...

Ayelet Fishman - One of the best experts on this subject based on the ideXlab platform.

  • the unravelling of the complex pattern of Tyrosinase inhibition
    Scientific Reports, 2016
    Co-Authors: Batel Deri, Mor Goldfeder, M Kanteev, Noam Adir, Daniel Lecina, Victor Guallar, Ayelet Fishman
    Abstract:

    Tyrosinases are responsible for melanin formation in all life domains. Tyrosinase inhibitors are used for the prevention of severe skin diseases, in skin-whitening creams and to avoid fruit browning, however continued use of many such inhibitors is considered unsafe. In this study we provide conclusive evidence of the inhibition mechanism of two well studied Tyrosinase inhibitors, KA (kojic acid) and HQ (hydroquinone), which are extensively used in hyperpigmentation treatment. KA is reported in the literature with contradicting inhibition mechanisms, while HQ is described as both a Tyrosinase inhibitor and a substrate. By visualization of KA and HQ in the active site of TyrBm crystals, together with molecular modeling, binding constant analysis and kinetic experiments, we have elucidated their mechanisms of inhibition, which was ambiguous for both inhibitors. We confirm that while KA acts as a mixed inhibitor, HQ can act both as a TyrBm substrate and as an inhibitor.

  • determination of Tyrosinase substrate binding modes reveals mechanistic differences between type 3 copper proteins
    Nature Communications, 2014
    Co-Authors: Mor Goldfeder, M Kanteev, Sivan Isascharovdat, Noam Adir, Ayelet Fishman
    Abstract:

    Tyrosinases mediate the initial two catalytic steps in the conversion of tyrosine into melanin, and mutations in these enzymes are leading causes of albinism. Goldfeder et al. present Tyrosinase crystal structures and reveal that both of its substrates orient identically in the active site.

  • determination of Tyrosinase substrate binding modes reveals mechanistic differences between type 3 copper proteins
    Nature Communications, 2014
    Co-Authors: Mor Goldfeder, M Kanteev, Sivan Isascharovdat, Noam Adir, Ayelet Fishman
    Abstract:

    Tyrosinase is responsible for the two initial enzymatic steps in the conversion of tyrosine to melanin. Many Tyrosinase mutations are the leading cause of albinism in humans, and it is a prominent biotechnology and pharmaceutical industry target. Here we present crystal structures that show that both monophenol hydroxylation and diphenol oxidation occur at the same site. It is suggested that concurrent presence of a phenylalanine above the active site and a restricting thioether bond on the histidine coordinating CuA prevent hydroxylation of monophenols by catechol oxidases. Furthermore, a conserved water molecule activated by E195 and N205 is proposed to mediate deprotonation of the monophenol at the active site. Overall, the structures reveal precise steps in the enzymatic catalytic cycle as well as differences between Tyrosinases and other type-3 copper enzymes.

  • Changes in Tyrosinase specificity by ionic liquids and sodium dodecyl sulfate
    Applied Microbiology and Biotechnology, 2013
    Co-Authors: Mor Goldfeder, Noam Adir, Mor Egozy, Vered Shuster Ben-yosef, Ayelet Fishman
    Abstract:

    Tyrosinase is a member of the type 3 copper enzyme family involved in the production of melanin in a wide range of organisms. The ability of Tyrosinases to convert monophenols into diphenols has stimulated studies regarding the production of substituted catechols, important intermediates for the synthesis of pharmaceuticals, agrochemicals, polymerization inhibitors, and antioxidants. Despite its enormous potential, the use of Tyrosinases for catechol synthesis has been limited due to the low monophenolase/diphenolase activity ratio. In the presence of two water miscible ionic liquids, [BMIM][BF_4] and ethylammonium nitrate, the selectivity of a Tyrosinase from Bacillus megaterium (TyrBm) was altered, and the ratio of monophenolase/diphenolase activity increased by up to 5-fold. Furthermore, the addition of sodium dodecyl sulphate (SDS) at levels of 2–50 mM increased the activity of TyrBm by 2-fold towards the natural substrates l -tyrosine and l -Dopa and 15- to 20-fold towards the non-native phenol and catechol. The R209H Tyrosinase variant we previously identified as having a preferential ratio of monophenolase/diphenolase activity was shown to have a 45-fold increase in activity towards phenol in the presence of SDS. We propose that the effect of SDS on the ability of Tyrosinase to convert non-natural substrates is due to the interaction of surfactant molecules with residues located at the entrance to the active site, as visualized by the newly determined crystal structure of TyrBm in the presence of SDS. The effect of SDS on R209 may enable less polar substrates such as phenol and catechol, to penetrate more efficiently into the enzyme catalytic pocket.

Wen Shi - One of the best experts on this subject based on the ideXlab platform.

  • detection of misdistribution of Tyrosinase from melanosomes to lysosomes and its upregulation under psoralen ultraviolet a with a melanosome targeting Tyrosinase fluorescent probe
    Analytical Chemistry, 2016
    Co-Authors: Jin Zhou, Wen Shi, Qiuyu Gong
    Abstract:

    Tyrosinase is regarded as an important biomarker of melanoma cancer, and its metabolism is closely related to some severe skin diseases such as vitiligo. Since Tyrosinase is mainly located in the melanosomes of melanocytes, a probe that can specifically detect and image tysosinase in melanosomes would be in urgent demand to study the behavior of the enzyme in cells, but unfortunately, no melanosome-targeting Tyrosinase fluorescent probe has been reported so far to the best of our knowledge. In this work, we have developed such a new probe, Mela-TYR, which bears morpholine as a melanosome-targeting group and 4-aminophenol as a Tyrosinase reaction group. The probe exhibits not only a highly sensitive and selective off-on response to Tyrosinase via oxidization cleavage, but also an accurate targeting ability toward the acidic organelles of melanosomes and lyososomes, which is validated by colocalization experiments with mCherry-tagged melanosomes as well as DND-99 (a commercial dye). The probe has been used ...

  • Detection of Misdistribution of Tyrosinase from Melanosomes to Lysosomes and Its Upregulation under Psoralen/Ultraviolet A with a Melanosome-Targeting Tyrosinase Fluorescent Probe.
    Analytical chemistry, 2016
    Co-Authors: Jin Zhou, Wen Shi, Qiuyu Gong
    Abstract:

    Tyrosinase is regarded as an important biomarker of melanoma cancer, and its metabolism is closely related to some severe skin diseases such as vitiligo. Since Tyrosinase is mainly located in the melanosomes of melanocytes, a probe that can specifically detect and image tysosinase in melanosomes would be in urgent demand to study the behavior of the enzyme in cells, but unfortunately, no melanosome-targeting Tyrosinase fluorescent probe has been reported so far to the best of our knowledge. In this work, we have developed such a new probe, Mela-TYR, which bears morpholine as a melanosome-targeting group and 4-aminophenol as a Tyrosinase reaction group. The probe exhibits not only a highly sensitive and selective off-on response to Tyrosinase via oxidization cleavage, but also an accurate targeting ability toward the acidic organelles of melanosomes and lyososomes, which is validated by colocalization experiments with mCherry-tagged melanosomes as well as DND-99 (a commercial dye). The probe has been used ...

Mor Goldfeder - One of the best experts on this subject based on the ideXlab platform.

  • the unravelling of the complex pattern of Tyrosinase inhibition
    Scientific Reports, 2016
    Co-Authors: Batel Deri, Mor Goldfeder, M Kanteev, Noam Adir, Daniel Lecina, Victor Guallar, Ayelet Fishman
    Abstract:

    Tyrosinases are responsible for melanin formation in all life domains. Tyrosinase inhibitors are used for the prevention of severe skin diseases, in skin-whitening creams and to avoid fruit browning, however continued use of many such inhibitors is considered unsafe. In this study we provide conclusive evidence of the inhibition mechanism of two well studied Tyrosinase inhibitors, KA (kojic acid) and HQ (hydroquinone), which are extensively used in hyperpigmentation treatment. KA is reported in the literature with contradicting inhibition mechanisms, while HQ is described as both a Tyrosinase inhibitor and a substrate. By visualization of KA and HQ in the active site of TyrBm crystals, together with molecular modeling, binding constant analysis and kinetic experiments, we have elucidated their mechanisms of inhibition, which was ambiguous for both inhibitors. We confirm that while KA acts as a mixed inhibitor, HQ can act both as a TyrBm substrate and as an inhibitor.

  • determination of Tyrosinase substrate binding modes reveals mechanistic differences between type 3 copper proteins
    Nature Communications, 2014
    Co-Authors: Mor Goldfeder, M Kanteev, Sivan Isascharovdat, Noam Adir, Ayelet Fishman
    Abstract:

    Tyrosinases mediate the initial two catalytic steps in the conversion of tyrosine into melanin, and mutations in these enzymes are leading causes of albinism. Goldfeder et al. present Tyrosinase crystal structures and reveal that both of its substrates orient identically in the active site.

  • determination of Tyrosinase substrate binding modes reveals mechanistic differences between type 3 copper proteins
    Nature Communications, 2014
    Co-Authors: Mor Goldfeder, M Kanteev, Sivan Isascharovdat, Noam Adir, Ayelet Fishman
    Abstract:

    Tyrosinase is responsible for the two initial enzymatic steps in the conversion of tyrosine to melanin. Many Tyrosinase mutations are the leading cause of albinism in humans, and it is a prominent biotechnology and pharmaceutical industry target. Here we present crystal structures that show that both monophenol hydroxylation and diphenol oxidation occur at the same site. It is suggested that concurrent presence of a phenylalanine above the active site and a restricting thioether bond on the histidine coordinating CuA prevent hydroxylation of monophenols by catechol oxidases. Furthermore, a conserved water molecule activated by E195 and N205 is proposed to mediate deprotonation of the monophenol at the active site. Overall, the structures reveal precise steps in the enzymatic catalytic cycle as well as differences between Tyrosinases and other type-3 copper enzymes.

  • Changes in Tyrosinase specificity by ionic liquids and sodium dodecyl sulfate
    Applied Microbiology and Biotechnology, 2013
    Co-Authors: Mor Goldfeder, Noam Adir, Mor Egozy, Vered Shuster Ben-yosef, Ayelet Fishman
    Abstract:

    Tyrosinase is a member of the type 3 copper enzyme family involved in the production of melanin in a wide range of organisms. The ability of Tyrosinases to convert monophenols into diphenols has stimulated studies regarding the production of substituted catechols, important intermediates for the synthesis of pharmaceuticals, agrochemicals, polymerization inhibitors, and antioxidants. Despite its enormous potential, the use of Tyrosinases for catechol synthesis has been limited due to the low monophenolase/diphenolase activity ratio. In the presence of two water miscible ionic liquids, [BMIM][BF_4] and ethylammonium nitrate, the selectivity of a Tyrosinase from Bacillus megaterium (TyrBm) was altered, and the ratio of monophenolase/diphenolase activity increased by up to 5-fold. Furthermore, the addition of sodium dodecyl sulphate (SDS) at levels of 2–50 mM increased the activity of TyrBm by 2-fold towards the natural substrates l -tyrosine and l -Dopa and 15- to 20-fold towards the non-native phenol and catechol. The R209H Tyrosinase variant we previously identified as having a preferential ratio of monophenolase/diphenolase activity was shown to have a 45-fold increase in activity towards phenol in the presence of SDS. We propose that the effect of SDS on the ability of Tyrosinase to convert non-natural substrates is due to the interaction of surfactant molecules with residues located at the entrance to the active site, as visualized by the newly determined crystal structure of TyrBm in the presence of SDS. The effect of SDS on R209 may enable less polar substrates such as phenol and catechol, to penetrate more efficiently into the enzyme catalytic pocket.