Cav1.2钙离子通道三维结构的同源建模及其应用  

Homology modeling and application of 3D structure of Cav1.2 channel

作　　者：雷明[1] 苏敬阳[1] 李卓[1] 晏珊[1] 孙雪菲[1] 朱彤[2] 郝丽英[1] 

机构地区：[1]中国医科大学药学院药物毒理教研室,辽宁沈阳110122 [2]东北大学环境生物学教研室,辽宁沈阳110004

出　　处：《中国药理学通报》2017年第1期90-94,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 31471091)

摘　　要：目的构建心肌Cav1.2钙离子通道三维结构模型,检验模型的准确性与可靠性。方法利用SWISS-MODEL同源建模服务器,对豚鼠心肌细胞Cav1.2通道α1亚基进行同源建模,建模结果提交至加州大学蛋白质结构在线检测服务器进行检测评估,并对结构模型进行打分。利用MOE软件分子对接程序模拟阻断剂或药物与Cav1.2通道模型的结合,进一步验证通道模型的准确性与可靠性。结果在SWISS-MODEL服务器上搜寻到的模板序列Cav1.1α1S与目标序列Cav1.2α1C均为L型钙通道,序列比对结果显示其同源性高达71.5%,选择自动模式(automated mode)进行同源建模。L型钙通道阻断剂维拉帕米、硝苯地平、地尔硫卓能结合到Cav1.2通道三维结构模型的特定区域,而钠通道特异性阻断剂河豚毒素并未与该模型相结合,中药有效成份白花前胡甲素和小檗碱与该模型也有一定的结合。结论成功构建了心肌Cav1.2钙离子通道三维结构模型,为后续研究提供了可靠样本,也为同源建模在研究离子通道三维结构预测中的应用奠定了基础。Aim To construct 3D structure model of cardiac Cav1. 2 channel and check its accuracy and reliability. Methods Homology model of Cav1. 2 channel α1 subunit was constructed using SWISS-MODEL server. The model was submitted to an online testing server built by University of California and scored by it. The binding of Cav1. 2 channel with blocker or drug was simulated by MOE software molecular docking program to check the model＇s accuracy and reliability. Results Both the target sequence Cav1. 2 α1C and the template sequence Cav1. 1 α1S searched by SWISSMODEL server belonged to L-type Ca^（2＋）channel. Since the homology was 71. 5% revealed by sequence alignment,homology modeling was performed using automated mode. L-type Ca^（2＋）channel blockers Verapamil,Nifedipine and Diltiazem could bind to the 3D structure model of Cav1. 2 channel,while sodium channel blocker TTX could not. Furthermore,active ingredient of traditional Chinese drug Praeruptorin A and Berberine could also bind to the 3D structure model of Cav1. 2channel. Conclusion The 3D structure model of Cav1. 2 channel was constructed successfully,which provides reliable materials for further studies and establishes the foundation for the application of homology modeling in the study of 3D structure prediction of ion channels.

关 键 词：离子通道 三维结构 同源建模 MOE软件 L型钙通道阻断剂 分子对接 

分 类 号：R322.11[医药卫生—人体解剖和组织胚胎学] R329.25[医药卫生—基础医学]