Inhibitory effect of acarbose on tyrosinase: application of molecular dynamics integrating inhibition kinetics

Abstract

Due to its clinical and cosmetic applications, investigators have paid attention to tyrosinase (TYR) inhibitor development. In this study, a TYR inhibition study with acarbose was investigated to gain insights into the regulation of the catalytic function. Biochemical assay results indicated that acarbose was turned to be an inhibitor of TYR in a reversible binding manner and probed as a distinctive mixed-type inhibitor via measurement of double-reciprocal kinetic (K_i = 18.70 ± 4.12 mM). Time-interval kinetic measurement indicated that TYR catalytic function was gradually inactivated by acarbose in a time-dependent behavior displaying with a monophase process that was evaluated by semi-logarithmic plotting. Spectrofluorimetric measurement by integrating with a hydrophobic residue detector (1-anilinonaphthalene-8-sulfonate) showed that the high dose of acarbose derived a conspicuous local structural deformation of the TYR catalytic site pocket. Computational docking simulation showed that acarbose bound to key residues such as HIS61, TYR65, ASN81, HIS244, and HIS259. Our study extends an understanding of the functional application of acarbose and proposes that acarbose is an alternative candidate drug for a whitening agent via direct retardation of TYR catalytic function and it would be applicable for the relevant skin hyperpigmentation disorders concerning the dermatologic clinical purpose.

Communicated by Ramaswamy H. Sarma

Keywords:

• Tyrosinase
• acarbose
• inhibitor
• kinetics
• molecular docking

Disclosure statement

The authors declare that they have no conflicts of interest.

Additional information

Funding

This work was supported by the Key Scientific and Technological Grant of Zhejiang for Breeding New Agricultural Varieties [2021C02069-8-3], the Zhejiang Province Welfare Technology Applied Research Project [LGN21C190013, LGN22C190022], and Key Technology Research and Development Projects in Ningbo [2021Z009]. Jinhyuk Lee was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education [NRF-2020R1I1A2071859] and the Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program [KGM5362111].