title: New tyrosinase inhibitory decapeptide: Molecular insights into the role of tyrosine residues.
abstract: Tyrosinase, a rate-limiting enzyme in melanin biosynthesis, catalyzes the hydroxylation of l-tyrosine to 3,4-dihydroxy-l-phenylalanine (l-dopa) (monophenolase reaction) and the subsequent oxidation of l-dopa to l-dopaquinone (diphenolase reaction). Thus, tyrosinase inhibitors have been proposed as skin-lightening agents; however, many of the existing inhibitors cannot be widely used in the cosmetic industry due to their high cytotoxicity and instability. On the other hand, some tyrosinase inhibitory peptides have been reported as safe. In this study, we found that the peptide TH10, which has a similar sequence to the characterized inhibitory peptide P4, strongly inhibits the monophenolase reaction with a half-maximal inhibitory concentration of 102 μM. Seven of the ten amino acid residues in TH10 were identical to P4; however, TH10 possesses one N-terminal tyrosine, whereas P4 contains three tyrosine residues located at its N-terminus, center, and C-terminus. Subsequent analysis using sequence-shuffled variants indicated that the tyrosine residues located at the N-terminus and center of P4 have little to no contribution to its inhibitory activity. Furthermore, docking simulation analysis of these peptides with mushroom tyrosinase demonstrated that the active tyrosine residue was positioned close to copper ions, suggesting that TH10 and P4 bind to tyrosinase as a substrate analogue.
authors.affiliation: Department of Materials Science and Technology, Faculty of Engineering, Niigata University, Niigata 950-2181, Japan; Graduate School of Science and Technology, Niigata University, Niigata 950-2181, Japan. Electronic address: ottie@eng.niigata-u.ac.jp.
authors.forename: Akihito
authors.initials: A
authors.lastname: Ochiai
authors.affiliation: Graduate School of Science and Technology, Niigata University, Niigata 950-2181, Japan.
authors.forename: Seiya
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Graduate School of Science and Technology, Niigata University, Niigata 950-2181, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Imai
authors.affiliation: Graduate School of Science and Technology, Niigata University, Niigata 950-2181, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Graduate School of Science and Technology, Niigata University, Niigata 950-2181, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Kanaoka
authors.affiliation: Department of Materials Science and Technology, Faculty of Engineering, Niigata University, Niigata 950-2181, Japan; Graduate School of Science and Technology, Niigata University, Niigata 950-2181, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Materials Science and Technology, Faculty of Engineering, Niigata University, Niigata 950-2181, Japan; Graduate School of Science and Technology, Niigata University, Niigata 950-2181, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Taniguchi
mesh_terms: D000363:Agaricales / Q000201:enzymology*; D003300:Copper / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006900:Hydroxylation; D007700:Kinetics; D007980:Levodopa / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D008543:Melanins; D009842:Oligopeptides; C560821:peptide P4; C000614939:peptide TH10; D014443:Tyrosine; D007980:Levodopa; D003300:Copper; D010088:Oxidoreductases; C412191:monophenolase; D014442:Monophenol Monooxygenase
keywords: Action mechanism; Melanogenesis; Peptide; Skin-lightening agents; Tyrosinase inhibitor