Department of Food Engineering, Faculty of Engineering, Iğdır University, Iğdır, Turkey.
Vocational School of Technical Sciences, Department of Chemistry and Chemical Processing Technologies, Iğdır University, Iğdır, Turkey.
J Biomol Struct Dyn. 2022 Oct;40(17):7926-7939. doi: 10.1080/07391102.2021.1905069. Epub 2021 Mar 29.
The present study aims to investigate the substrate (4-methyl catechol and catechol) specificity and inhibition mechanisms (l-ascorbic acid, citric acid, and l-cysteine) of the tyrosinase enzyme (TYR), which is held responsible for browning in foods and hyperpigmentation in the human skin, through kinetic and molecular docking studies. During the experimental studies, the diphenolase activities of TYR were determined, following which the inhibitory effects of the inhibitors upon the diphenolase activities of TYR. The inhibition types were determined as competitively for l-ascorbic acid and citric acid and noncompetitive for l-cysteine. The kinetic results showed that the substrate specificity was better for catechol while l-cysteine showed the best inhibition profile. As for the studies, they also showed that catechol had a better affinity in line with the experimental results of this study, considering the interactions of the substrates with TYR's active site residues and their distance to CuB metal ion, which is an indicator of diphenolase activity. Besides, the inhibitory mechanisms of the inhibitor molecules were explained by the molecular modeling studies, considering the binding number of the inhibitors with the active site amino acid residues of TYR, the number and length of H bonds, negative binding energy values, and their distance to CuB metal ion. Based on our results, we suggest that the novel method used in this study to explain the inhibitory mechanism of l-cysteine may provide an affordable alternative to the expensive methods available for explaining the inhibitory mechanism of TYR and those of other enzymes. HighlightsThe best affinity for the tyrosinase enzyme occurred with catechol.l-Ascorbic acid, citric acid, l-cysteine inhibited the diphenolic activity of tyrosinase. studies confirmed the best affinity shown by catechol.Product inhibition mechanism of l-cysteine explained by for the first time.Communicated by Ramaswamy H. Sarma.
本研究旨在通过动力学和分子对接研究，探讨与食品褐变和人体皮肤色素沉着有关的酪氨酸酶（TYR）的底物（对甲基儿茶酚和儿茶酚）特异性和抑制机制（抗坏血酸、柠檬酸和半胱氨酸）。在实验研究中，测定了 TYR 的二酚酶活性，然后测定了抑制剂对 TYR 的二酚酶活性的抑制作用。抑制类型被确定为抗坏血酸和柠檬酸的竞争性，半胱氨酸为非竞争性。动力学结果表明，对儿茶酚的底物特异性更好，而半胱氨酸表现出最佳的抑制特性。此外，研究还表明，考虑到底物与 TYR 活性位点残基的相互作用及其与 CuB 金属离子的距离，即二酚酶活性的指标，儿茶酚具有更好的亲和力，这与本研究的实验结果一致。此外，通过分子建模研究解释了抑制剂分子的抑制机制，考虑到抑制剂与 TYR 活性位点氨基酸残基的结合数、氢键的数量和长度、负结合能值及其与 CuB 金属离子的距离。基于我们的结果，我们建议本研究中用于解释半胱氨酸抑制机制的新方法可能为解释 TYR 和其他酶的抑制机制提供一种经济实惠的替代方案，这些方法昂贵且难以获得。 要点TYR 对儿茶酚的亲和力最佳。抗坏血酸、柠檬酸、半胱氨酸抑制酪氨酸酶的二酚活性。研究首次通过 证实了儿茶酚表现出的最佳亲和力。首次解释了半胱氨酸的产物抑制机制。 通讯作者：Ramaswamy H. Sarma。
