Abstract

In the vertebrates, including fish, the tyrosinase enzyme plays an essential role in coloration. Modulation of tyrosinase activity is expected to alter the body pigmentation in fish and other vertebrate species. In the present study, physicochemical, functional, and structural properties of tyrosinase of three fish species viz., goldfish, Japanese medaka, and common carp were determined. The homology model was developed using the Chimera1.1.2, Swiss model, and Phyre2, and the best model was selected upon evaluation. Further, a virtual screening method was applied to identify the putative modulators using the PyRx- Virtual screening tool. The estimated physicochemical and functional properties of tyrosinase from the three species suggested that they all are hydrophobic, acidic, thermostable, with a high extinction coefficient (Cys, Trp, and Tyr) and have transmembrane-segment. Based on virtual screening against 13,000 compounds from the zinc database, five compounds were determined as potent modulators of fish tyrosinase with a binding energy of −7.0 to −8.8 Kcal/mol. Of these, Pilosine (ZINC13469966) was found to be the best putative modulator with low binding energy and properties of standardized drugs. This study showed that the tyrosinase function could be modulated to alter the pigment formation in fish species by using small compound.

摘要

在包括鱼类在内的脊椎动物中，酪氨酸酶在着色中起着至关重要的作用。预计酪氨酸酶活性的调节会改变鱼类和其他脊椎动物物种的身体色素沉着。在本研究中，三种鱼类的酪氨酸酶的物理化学、功能和结构特性，即.，金鱼、日本青鳉和鲤鱼被确定。使用Chimera1.1.2、Swiss模型和Phyre2开发同源模型，经评估选出最佳模型。此外，使用 PyRx-Virtual 筛选工具应用虚拟筛选方法来识别推定的调节剂。来自这三个物种的酪氨酸酶的估计物理化学和功能特性表明它们都是疏水的、酸性的、热稳定的、具有高消光系数（Cys、Trp和Tyr）并且具有跨膜片段。基于对锌数据库中 13,000 种化合物的虚拟筛选，确定了 5 种化合物作为鱼酪氨酸酶的有效调节剂，结合能为 -7.0 至 -8.8 Kcal/mol。这些，Pilosine (ZINC13469966) 被发现是具有低结合能和标准化药物特性的最佳推定调节剂。这项研究表明，可以通过使用小化合物来调节酪氨酸酶功能以改变鱼类的色素形成。