International Journal of Pharmacy and Pharmacology

ISSN 2326-7267

International Journal of Pharmacy and Pharmacology ISSN: 2326-7267 Vol. 9 (8), pp. 001-011, August, 2020. © International Scholars Journals

Full Length Research Paper

Computational simulations integrating inhibition kinetics of tyrosinase by oxalic acid

Li Yan1, Shang-Jun Yin2, Daeui Park3, Yue-Xiu Si2, Zhi-Jiang Wang2, Hae Young Chung3, Jun-Mo Yang4, *Guo-Ying Qian2, *Yong-Doo Park1,2

1Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, P. R. China.

2College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, P. R. China.

3Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, Korea.

4Department of Dermatology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul 135-710, Korea.

Accepted 19 April, 2020

Abstract

Tyrosinase inhibition studies are important for agricultural and medicinal applications. Computational predictions and enzymatic assays via kinetics may be used to detect effective inhibitors of tyrosinase. We predicted the 3D structure of tyrosinase from Agaricus bisporus, used a docking algorithm to simulate binding between tyrosinase and oxalic acid (OA), and studied the reversible inhibition of tyrosinase by OA. Simulations were successful (binding energies for Dock6.3 = -18.76 and AutoDock4.2 = -2.47 kcal/mol), suggesting that OA interacts with the LYS224 residue that is predicted by both programs. OA inhibited tyrosinase in a mixed-type manner with a Ki = 3.16 ± 1.8 mM and IC50 = 8.0 ± 0.5 mM. Measurements of intrinsic and ANS-binding fluorescences showed that OA induced changes in the active site structure. Our results suggest that the strategy of predicting tyrosinase inhibition based on carboxyl groups and orientation may prove useful for the screening of potential tyrosinase inhibitors.

Key Words: Tyrosinase, oxalic acid, docking simulation, inhibition kinetics, mixed-type, carboxyl group

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Shang-Jun Yin on Google Scholar Shang-Jun Yin on Pubmed Jun-Mo Yang on Google Scholar Jun-Mo Yang on Pubmed Yue-Xiu Si on Google Scholar Yue-Xiu Si on Pubmed Hae Young Chung on Google Scholar Hae Young Chung on Pubmed Li Yan on Google Scholar Li Yan on Pubmed Zhi-Jiang Wang on Google Scholar Zhi-Jiang Wang on Pubmed Daeui Park on Google Scholar Daeui Park on Pubmed *Guo-Ying Qian and *Yong-Doo Park on Google Scholar *Guo-Ying Qian and *Yong-Doo Park on Pubmed