A novel method for explaining the product inhibition mechanisms via molecular docking: inhibition studies for tyrosinase from Agaricus bisporus

• Published in: Journal of biomolecular structure & dynamics Vol. 40; no. 17; pp. 7926 - 7939
• Main Authors: Kaya, Elif Duygu, Türkhan, Ayşe, Gür, Fatma, Gür, Bahri
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 22.11.2022
• Subjects: diphenolase activity; molecular docking; negative binding energy; product inhibition; Tyrosinase; negative binding energy; product inhibition; molecular docking; diphenolase activity; Tyrosinase
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2021.1905069

The present study aims to investigate the substrate (4-methyl catechol and catechol) specificity and inhibition mechanisms (l-ascorbic acid, citric acid, and l-cysteine) of the tyrosinase enzyme (TYR), which is held responsible for browning in foods and hyperpigmentation in the human skin, through kinetic and molecular docking studies. During the experimental studies, the diphenolase activities of TYR were determined, following which the inhibitory effects of the inhibitors upon the diphenolase activities of TYR. The inhibition types were determined as competitively for l-ascorbic acid and citric acid and noncompetitive for l-cysteine. The kinetic results showed that the substrate specificity was better for catechol while l-cysteine showed the best inhibition profile. As for the in silico studies, they also showed that catechol had a better affinity in line with the experimental results of this study, considering the interactions of the substrates with TYR's active site residues and their distance to CuB metal ion, which is an indicator of diphenolase activity. Besides, the inhibitory mechanisms of the inhibitor molecules were explained by the molecular modeling studies, considering the binding number of the inhibitors with the active site amino acid residues of TYR, the number and length of H bonds, negative binding energy values, and their distance to CuB metal ion. Based on our results, we suggest that the novel method used in this study to explain the inhibitory mechanism of l-cysteine may provide an affordable alternative to the expensive methods available for explaining the inhibitory mechanism of TYR and those of other enzymes. Highlights The best affinity for the tyrosinase enzyme occurred with catechol. l-Ascorbic acid, citric acid, l-cysteine inhibited the diphenolic activity of tyrosinase. In silico studies confirmed the best affinity shown by catechol. Product inhibition mechanism of l-cysteine explained by in silico for the first time. Communicated by Ramaswamy H. Sarma