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. 2022 Mar 19;23(6):3335.
doi: 10.3390/ijms23063335.

Theoretical Studies of Cyanophycin Dipeptides as Inhibitors of Tyrosinases

Agnieszka Krzemińska  1 , Natalia Kwiatos  1 , Franciela Arenhart Soares  1 , Alexander Steinbüchel  1
Affiliations

Theoretical Studies of Cyanophycin Dipeptides as Inhibitors of Tyrosinases

Agnieszka Krzemińska et al. Int J Mol Sci. .

Abstract

The three-dimensional structure of tyrosinase has been crystallized from many species but not from Homo sapiens. Tyrosinase is a key enzyme in melanin biosynthesis, being an important target for melanoma and skin-whitening cosmetics. Several studies employed the structure of tyrosinase from Agaricus bisporus as a model enzyme. Recently, 98% of human genome proteins were elucidated by AlphaFold. Herein, the AlphaFold structure of human tyrosinase and the previous model were compared. Moreover, tyrosinase-related proteins 1 and 2 were included, along with inhibition studies employing kojic and cinnamic acids. Peptides are widely studied for their inhibitory activity of skin-related enzymes. Cyanophycin is an amino acid polymer produced by cyanobacteria and is built of aspartic acid and arginine; arginine can be also replaced by other amino acids. A new set of cyanophycin-derived dipeptides was evaluated as potential inhibitors. Aspartate-glutamate showed the strongest interaction and was chosen as a leading compound for future studies.

Keywords: AlphaFold; molecular docking; tyrosinase; tyrosinase-related protein 1; tyrosinase-related protein 2.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Proposed melanin biosynthesis involving the three tyrosinase-related proteins.
Figure 2
Figure 2
Pairwise sequence alignment of TYR and abTYR sequences used in this study. Magenta, CuA binding pattern; blue, CuB binding pattern; orange, EFG pattern.
Figure 3
Figure 3
Three-dimensional structures of tyrosinases: (A) TYR, (B) TYRP1, (C) TYRP2. Grey, tyrosinase domain; magenta, CuA binding pattern; blue, CuB binding pattern; orange, EFG pattern; brown, copper atoms; green, zinc atoms.
Figure 4
Figure 4
Maps of electrostatic potential for (A) Lig2, (B) Lig4, and (C) the active site of TYR.
See this image and copyright information in PMC

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