Lima Carlyle Ribeiro, Silva José Rogério A, de Tássia Carvalho Cardoso Erica, Silva Edilene O, Lameira Jerônimo, do Nascimento José Luiz Martins, do Socorro Barros Brasil Davi, Alves Cláudio N
Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, 66075-110 Belém, PA, Brazil.
Laboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, 66075-110 Belém, PA, Brazil.
Molecules. 2014 Jul 7;19(7):9591-605. doi: 10.3390/molecules19079591.
Tyrosinase is a key enzyme in melanin synthesis and widely distributed in plants and animals tissues. In mammals, this enzyme is related to pigment production, involved in wound healing, primary immune response and it can also contribute to catecholamines synthesis in the brain. Consequently, tyrosinase enzyme represents an attractive and selective target in the field of the medicine, cosmetics and bio-insecticides. In this paper, experimental kinetics and computational analysis were used to study the inhibition of tyrosinase by analogous of Kojic acid. The main interactions occurring between inhibitors-tyrosinase complexes and the influence of divalent cation (Cu2+) in enzymatic inhibition were investigated by using molecular docking, molecular dynamic simulations and electrostatic binding free energy by using the Linear Interaction Energy (LIE) method. The results showed that the electrostatic binding free energy are correlated with values of constant inhibition (r2 = 0.97).Thus, the model obtained here could contribute to future studies of this important system and, therefore, eventually facilitate development of tyrosinase inhibitors.
酪氨酸酶是黑色素合成中的关键酶，广泛分布于动植物组织中。在哺乳动物中，这种酶与色素生成有关，参与伤口愈合、初级免疫反应，还能促进大脑中儿茶酚胺的合成。因此，酪氨酸酶是医学、化妆品和生物杀虫剂领域中一个有吸引力的选择性靶点。本文采用实验动力学和计算分析方法研究了曲酸类似物对酪氨酸酶的抑制作用。通过分子对接、分子动力学模拟以及使用线性相互作用能（LIE）方法计算静电结合自由能，研究了抑制剂 - 酪氨酸酶复合物之间发生的主要相互作用以及二价阳离子（Cu2 +）对酶抑制作用的影响。结果表明，静电结合自由能与抑制常数的值相关（r2 = 0.97）。因此，此处获得的模型有助于该重要系统的未来研究，并最终促进酪氨酸酶抑制剂的开发。
