a Medicinal and Natural Products Chemistry Research Center , Shiraz University of Medical Sciences , Shiraz , Iran.
b Testing Calibration, Geotechnic & Technical Inspection Servies , Binaazma Sepahan Consulting Eng. Co. , Isfahan , Iran.
J Biomol Struct Dyn. 2018 Nov;36(15):4126-4142. doi: 10.1080/07391102.2017.1409651. Epub 2017 Dec 11.
Protein tyrosine phosphatase 1B (PTP1B) is a member of the PTP superfamily which is considered to be a negative regulator of insulin receptor (IR) signaling pathway. PTP1B is a promising drug target for the treatment of type 2 diabetes, obesity, and cancer. The existence of allosteric site in PTP1B has turned the researcher's attention to an alternate strategy for inhibition of this enzyme. Herein, the molecular interactions between the allosteric site of PTP1B with three non-competitive flavonoids, (MOR), (MOK), and (DPO) have been investigated. Three ligands were docked into allosteric site of the enzyme. The resulting protein-ligand complexes were used for molecular dynamics studies. Principal component and free-energy landscape (FEL) as well as cluster analyses were used to investigate the conformational and dynamical properties of the protein and identify representative enzyme substrates bounded to the inhibitors. Per residue energy decomposition analysis attributed dissimilar affinities of three inhibitors to the several hydrogen bonds and non-bonded interactions. In conclusion, our results exhibited an inhibitory pattern of the ligands against PTP1B.
蛋白酪氨酸磷酸酶 1B（PTP1B）是蛋白酪氨酸磷酸酶超家族的一员，被认为是胰岛素受体（IR）信号通路的负调节剂。PTP1B 是治疗 2 型糖尿病、肥胖症和癌症的有前途的药物靶点。PTP1B 存在别构位点，这引起了研究人员对抑制这种酶的另一种策略的关注。本文研究了 PTP1B 的别构位点与三种非竞争性黄酮类化合物（MOR）、（MOK）和（DPO）之间的分子相互作用。将三种配体对接入酶的别构位点。将所得的蛋白-配体复合物用于分子动力学研究。主成分分析和自由能景观（FEL）以及聚类分析用于研究蛋白质的构象和动力学特性，并确定与抑制剂结合的代表性酶底物。残基能量分解分析将三种抑制剂的不同亲和力归因于几个氢键和非键相互作用。总之，我们的结果显示了配体对 PTP1B 的抑制模式。
