Research Article Estimation of Inhibitory Effect against Tyrosinase Activity through Homology Modeling and Molecular Docking Daungkamon Nokinsee, 1 Lalida Shank, 1 Vannajan Sanghiran Lee, 2 and Piyarat Nimmanpipug 1 1 Computational Simulation and Modelling Laboratory (CSML), Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Tailand 2 Drug Design and Development Research Group, Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia Correspondence should be addressed to Piyarat Nimmanpipug; piyarat.n@cmu.ac.th Received 16 July 2015; Revised 15 October 2015; Accepted 2 November 2015 Academic Editor: David Ballou Copyright © 2015 Daungkamon Nokinsee et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Tyrosinase is a key enzyme in melanogenesis. Generally, mushroom tyrosinase from A. bisporus had been used as a model in skin- whitening agent tests employed in the cosmetic industry. Te recently obtained crystal structure of bacterial tyrosinase from B. megaterium has high similarity (33.5%) to the human enzyme and thus it was used as a template for constructing of the human model. Binding of tyrosinase to a series of its inhibitors was simulated by automated docking calculations. Docking and MD simulation results suggested that N81, N260, H263, and M280 are involved in the binding of inhibitors to mushroom tyrosinase. E195 and H208 are important residues in bacterial tyrosinase, while E230, S245, N249, H252, V262, and S265 bind to inhibitors and are important in forming pi interaction in human tyrosinase. 1. Introduction Tyrosinase is a metalloprotein belonging to type 3 copper enzyme family. It is involved in melanin production in a wide range of organisms. Te enzyme has a bifunctional catalytic mechanism consisting of the hydroxylation of monophenols to o-diphenols (monophenolase or cresolase activity) and the oxidation of o-diphenols to o-quinones (diphenolase or catecholase activity). Polymerization of products leads to melanin formation [1–3]. Tyrosinase is classifed into three diferent oxidation states with diferent functions. Each copper atom for all forms is coordinated by three histidine residues. Te frst, oxy-form (oxy-tyrosinase or E oxy : [Cu(II)– O 2 2− –Cu(II)]) tyrosinase contains two tetragonal copper(II) ions, and dioxygen is bound as a peroxide molecule and acts as a bridge between two copper ions, in the oxidation state, and can react with monophenol or diphenol substrate. Te oxy-tyrosinase can be obtained from met-tyrosinase by addition of hydrogen peroxide and deoxy-tyrosinase can be generated by binding to dioxygen. Te met-form (met- tyrosinase or E met : [Cu(II)–Cu(II)]) tyrosinase contains two tetragonal copper(II) ions similar to oxy-tyrosinase and can react with diphenol to produce o-quinone. Te met- tyrosinase can be converted to deoxy-tyrosinase by reducing copper(II) ions to copper(I) ions. Last, deoxy-form (deoxy- tyrosinase or E deoxy : [Cu(I)–Cu(I)]) tyrosinase can bind oxygen molecule and be reduced to oxy-form [4–6]. Te active site of tyrosinase is characterized by two copper atoms (CuA and CuB) that are surrounded by a bundle of 4 helices and coordinated by six histidine residues. Copper is essential for the catalytic activity of tyrosinase. Te active site is well conserved in diverse species [7]. Tyrosinase is a key enzyme in melanogenesis, which is essential for pigmentation. Te catalysis of L-tyrosine to L- dopa is the rate-limiting step of the enzymatic pathway in melanin formation. Tyrosinase is also an important factor in wound healing and cuticle formation in arthropods and browning in plants [8–10]. In humans, melanin helps protect Hindawi Publishing Corporation Enzyme Research Volume 2015, Article ID 262364, 12 pages http://dx.doi.org/10.1155/2015/262364