A 3D-structural modei of memapsin 2 protease generated from theoretical study  

用理论方法建立memapsin 2蛋白酶的三维结构模型(英文)

作　　者：黄小琴[1] 蒋华良[1] 罗小民[1] 沈竞康[1] 陈凯先[1] 嵇汝运[1] 曹阳[2] 薛红[3] 

机构地区：[1]中国科学院上海生命科学研究院上海药物研究所,上海中国200031 [2]苏州大学化学系,苏州中国215006 [3]香港科学技术大学生物化学系

出　　处：《Acta Pharmacologica Sinica》2001年第1期52-58,共7页中国药理学报（英文版）

基　　金：National Natural Science Foundation of China (№ 29725203);State Key Program of Basic Ressearch of China (№ 1998051115)

摘　　要：AIM: To build a 3D-structural model of memapsin 2 (M2) protease for theoretical study and drug design. METHODS: Structural alignment was performed based on multiple and pairwise sequence alignment of three templates. After the initial model was generated, energy minimization was completed by applying molecular mechanics method. Molecular dynamics (MD) technique was used to do further structural optimization. RESULTS: The 3D-structural model of memapsin 2 was constructed. The model is reasonable according to several validation criteria. The active-site motifs of M2 are structurally supported by a β-sheet rich domain and linked together with this domain through a helices. Tyrl32 contained in β-hairpin is a general characteristic of aspar-tic protease. The Ca atom superimposing result is a direct verification that M2 is structurally unique but still belongs to the aspartic protease superfamily. CONCLUSION: The 3D-structure model from our study is informative to guide future molecular biology study about M2 and drug design based on database searching.目的:通过理论方法建立M2蛋白酶的三维结构模型。方法:基于模板进行多重序列联配和结构联配建立M2蛋白酶的初始结构模型,对初始模型进行分子力学和分子动力学优化,用多种评价方法对所得结构进行合理评价。结果:得到了M2蛋白酶的三维结构模型,合理性评价结果表明该结构模型正确,M2蛋白酶的催化活性位点与天冬氨酸蛋白酶相似,区别在于与活性位点相邻的结构域的构象不同。结构保守区α碳原子叠合结果说明M2蛋白酶与其他天冬氨酸蛋白酶具有相同的生物进化来源。结论:M2蛋白酶的结构模型可以为进一步的分子生物学实验提供有益的参考,也可以此模型为基础进行数据库筛选和药物分子设计。

关 键 词：Alzheimer disease amyloid β-protein templates drug design 

分 类 号：R914[医药卫生—药物化学]