Determination of tyrosinase-cyanidin-3-O-glucoside and (-/ plus )-catechin binding modes reveal mechanistic differences in tyrosinase inhibition

0551538 - BTÚ 2022 RIV GB eng J - Journal Article
Lee, K. - Bharadwaj, Shiv - Sahoo, A. - Yadava, U. - Kang, S.
Determination of tyrosinase-cyanidin-3-O-glucoside and (-/ plus )-catechin binding modes reveal mechanistic differences in tyrosinase inhibition.
Scientific Reports. Roč. 11, č. 1 (2021), č. článku 24494. ISSN 2045-2322. E-ISSN 2045-2322
Institutional support: RVO:86652036
Keywords : mushroom tyrosinase * cyclic voltammetry * essential dynamics * melanin synthesis * crystal-structure
OECD category: 1.7 Other natural sciences
Impact factor: 4.997, year: 2021
Method of publishing: Open access
https://www.nature.com/articles/s41598-021-03569-1

Tyrosinase, exquisitely catalyzes the phenolic compounds into brown or black pigment, inhibition is used as a treatment for dermatological or neurodegenerative disorders. Natural products, such as cyanidin-3-O-glucoside and (-/+)-catechin, are considered safe and non-toxic food additives in tyrosinase inhibition but their ambiguous inhibitory mechanism against tyrosinase is still elusive. Thus, we presented the mechanistic insights into tyrosinase with cyanidin-3-O-glucoside and (-/+)-catechin using computational simulations and in vitro assessment. Initial molecular docking results predicted ideal docked poses (- 9.346 to 5.795 kcal/mol) for tyrosinase with selected flavonoids. Furthermore, 100 ns molecular dynamics simulations and post-simulation analysis of docked poses established their stability and oxidation of flavonoids as substrate by tyrosinase. Particularly, metal chelation via catechol group linked with the free 3-OH group on the unconjugated dihydropyran heterocycle chain was elucidated to contribute to tyrosinase inhibition by (-/+)-catechin against cyanidin-3-O-glucoside. Also, predicted binding free energy using molecular mechanics/generalized Born surface area for each docked pose was consistent with in vitro enzyme inhibition for both mushroom and murine tyrosinases. Conclusively, (-/+)-catechin was observed for substantial tyrosinase inhibition and advocated for further investigation for drug development against tyrosinase-associated diseases.
Permanent Link: http://hdl.handle.net/11104/0327327