长春碱与中心蛋白的结合及其对蛋白聚集性质的影响  

Binding of Vinblastine to Centrin and Effect on Its Aggregation Properties

作　　者：张文龙 胡颖媛 裴科 任蕾 杨斌盛[3] Zhang Wenlong;Hu Yingyuan;Pei Ke;Ren Lei;Yang Binsheng(College of Chinese Medicine and Food Engineering;Key Laboratory of Chinese Medicine Processing in Shanxi Province,Shanxi University of Chinese Medicine,Jinzhong,030619;Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education,Institue of Molecular Science,Shanxi University,Taiyuan,030006)

机构地区：[1]山西中医药大学中药与食品工程学院 [2]山西中医药大学中药炮制山西省重点实验室,晋中030619 [3]山西大学分子科学研究所化学生物学与分子工程教育部重点实验室,太原030006

出　　处：《化学通报》2023年第3期363-369,共7页Chemistry

基　　金：山西省自然科学基金项目(201901D211532);国家自然科学基金项目(81703704);山西省教育厅基金项目(2020L0416);山西中医药大学科研基金项目(2020BK09)资助。

摘　　要：通过光谱、等温滴定量热(ITC)以及分子对接等方法研究了八肋游仆虫中心蛋白N-端半分子(N-EoCen)与长春碱(Vin)之间的相互作用以及Vin对N-EoCen聚集性质的影响。结果表明,Vin可以与N-EoCen以摩尔比1∶1结合于N-EoCen的第一个EF-hand的F螺旋与第二个EF-hand的E、F螺旋之间,条件结合常数约为10^(4)L/mol。复合物的形成是放热的过程,主要依靠静电作用与疏水作用。N-EoCen与Vin结合后,构象发生变化,α螺旋含量减少,N-EoCen与Tb^(3+)结合能力减弱。最终使得N-EoCen的自聚集以及Tb^(3+)诱导的聚集减弱。研究结果为蛋白聚集抑制剂的筛选以及相关药物的研发提供了参考和依据。The interaction between vinblastine(Vin)and N-terminal domain of Euplotes octocarinatus centrin(N-EoCen)was described by spectroscopy,isothermal titration calorimetry(ITC)and molecular docking.Results showed that Vin could bind between the F helix of the first EF-hand and the E,F helix of the second EF-hand of N-EoCen with a molar ratio of 1∶1 stoichiometry in 10 mmol/L pH=7.4 Hepes buffer solution at room temperature.The conditional binding constant is about 10^(4) L/mol.The binding of Vin to N-EoCen is an exothermic process,mainly relying on electrostatic and hydrophobic interactions.The formation of N-EoCen-Vin complex leads to change of protein conformation and the decrease ofα-helix content as demonstrated by circular dichroism(CD)spectra and 3D fluorescence spectra.The binding ability of Tb^(3+)to N-EoCen is weakened upon complex formation.Finally,the binding of Vin to N-EoCen inhibits the self-aggregation and Tb^(3+)-induced aggregation of protein.The results provide a reference and basis for the screening of protein aggregation inhibitors and the development of related drugs.

关 键 词：中心蛋白 长春碱 复合物 聚集 抑制 

分 类 号：TQ464.7[化学工程—制药化工]