Abstract:Abstract: Sustained infection of high-risk human papilloma virus (HPV) leads to changes in the cell cycle of cervical epithelial cells and immune escape, eventually leading to cervical cancer. The ubiquitination of the tumor suppressor protein p53 by the E6 proteins from high-risk HPVs can be inhibited by the small molecule compounds reactivation of p53 and induction of tumor cell apoptosis (RITA) and curcumin, and the apoptotic function of HPV-positive cells can be restored, but the molecular mechanism of this phenomenon has not yet been elucidated. To analyze the binding modes of high-risk HPV oncogenic protein E6 and small molecule inhibitors RITA and curcumin, and to explore the feasibility of E6 protein as a drug target, the most common high-risk HPV subtypes, HPV16 and HPV18, were studied by homology modeling, molecu-lar docking and molecular dynamics simulation. The results showed that RITA and curcumin had a consistent conformation and a similar binding pattern in the hydrophobic groove which is formed by residues 41~49 of the HPV16/18 E6 protein. The phenylalanine residues that make up the hydrophobic groove and the aromatic rings of the two inhibitors played important roles in maintaining the conformation of the complex by hydrophobic interactions and π-π interactions. This research indicated the feasibility of the high-risk HPV E6 protein as a drug target, and may provide theoretical guidance for screening and designing cervical cancer-specific small molecule drugs.
引用本文:
张天一, 徐 苗, 丁 欢, 田菲菲. HPV16/18 E6蛋白与小分子抑制剂RITA和姜黄素的结合模式研究[J]. 生命科学研究, 2019, 23(5): 367-376.
ZHANG Tian-yi, XU Miao, DING Huan, TIAN Fei-fei. A Study on Binding Modes of HPV16/18 E6 Proteins with Small Molecule Inhibitors RITA and Curcumin. Life Science Research, 2019, 23(5): 367-376.