Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
J Biomol Struct Dyn. 2012;30(4):448-59. doi: 10.1080/07391102.2012.682210. Epub 2012 Jun 11.
Alterations in the synthesis of melanin contribute to a number of diseases; therefore, the design of new tyrosinase inhibitors is very important. Mushroom tyrosinase (MT) is a metalloenzyme, which plays an important role in melanin biosynthesis. In this study, the inhibitory effect of a novel designed compound, i.e. 2-((1Z)-(2-(2,4-dinitrophenyl)hydrazin-1-ylidene)methyl)phenol, as a specific ligand which can bind to the copper ion of MT, has been assessed. The ligand was found to competitively inhibit both the cresolase and catecholase activities of MT, with small inhibition constants of 2.8 and 2.6 μM, respectively. Intrinsic fluorescence studies were performed to gain more information on the binding constants. Docking results indicated that the ligand binds to copper ions in the active site of MT via the OH group of the ligand. The ligand makes four hydrogen bonds with aspartic acid and one hydrogen bond with the histidine residue in the active site. Molecular dynamics results show that ligand binds to the MT via both electrostatic and hydrophobic interactions with its different parts.
黑色素合成的改变导致了许多疾病；因此，设计新型酪氨酸酶抑制剂非常重要。蘑菇酪氨酸酶（MT）是一种金属酶，在黑色素生物合成中起着重要作用。在这项研究中，评估了一种新型设计化合物，即 2-((1Z)-(2-(2,4-二硝基苯基)肼-1-基)亚甲基)苯酚，作为可以与 MT 中的铜离子结合的特定配体的抑制作用。该配体被发现对 MT 的儿茶酚酶和苯酚酶活性均具有竞争性抑制作用，抑制常数分别为 2.8 和 2.6 μM。进行了本征荧光研究以获取有关结合常数的更多信息。对接结果表明，配体通过配体的 OH 基团与 MT 的活性位点中的铜离子结合。配体与活性位点中的天冬氨酸形成四个氢键，并与组氨酸残基形成一个氢键。分子动力学结果表明，配体通过其不同部分与 MT 之间的静电和疏水相互作用结合。
