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http://hdl.handle.net/10773/20484
Título: | Inulavosin and its benzo-derivatives, melanogenesis inhibitors, target the copper loading mechanism to the active site of tyrosinase |
Autor: | Fujita, Hideaki Menezes, Jose C. J. M. D. S. Santos, Sergio M. Yokota, Sadaki Kamat, Shrivallabh P. Cavaleiro, Jose A. S. Motokawa, Tomonori Kato, Tomomi Mochizuki, Mayu Fujiwara, Toshiyuki Fujii, Yuki Tanaka, Yoshitaka |
Palavras-chave: | SKIN PIGMENTATION MELANOSOME BIOGENESIS MELANIN SYNTHESIS PROTEINS PATHWAY DEGRADATION MELANOCYTES LYSOSOMES TRANSPORT BINDING |
Data: | 2014 |
Editora: | WILEY-BLACKWELL |
Resumo: | Tyrosinase, a melanosomal membrane protein containing copper, is a key enzyme for melanin synthesis in melanocytes. Inulavosin inhibits melanogenesis by enhancing a degradation of tyrosinase in lysosomes. However, the mechanism by which inulavosin redirects tyrosinase to lysosomes is yet unknown. The analyses of structure-activity relationship of inulavosin and its benzo-derivatives reveal that the hydroxyl and the methyl groups play a critical role in their inhibitory activity. Intriguingly, the docking studies to tyrosinase suggest that the compounds showing inhibitory activity bind through hydrophobic interactions to the cavity of tyrosinase below which the copper-binding sites are located. This cavity is proposed to be required for the association with a chaperon that assists in copper loading to tyrosinase in Streptomyces antibioticus. Inulavosin and its benzo-derivatives may compete with the copper chaperon and result in a lysosomal mistargeting of apo-tyrosinase that has a conformational defect. |
Peer review: | yes |
URI: | http://hdl.handle.net/10773/20484 |
DOI: | 10.1111/pcmr.12225 |
ISSN: | 1755-1471 |
Versão do Editor: | 10.1111/pcmr.12225 |
Aparece nas coleções: | CICECO - Artigos |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Inulavosin and its benzo-derivatives melanogenesis inhibitors target the copper loading mechanism to the active site of tyrosinase_10.1111pcmr.12225.pdf | 2.84 MB | Adobe PDF |
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