物理化学学报 >> 2008, Vol. 24 >> Issue (09): 1558-1562.doi: 10.1016/S1872-1508(08)60064-9

研究论文 上一篇    下一篇

含有D型氨基酸的新型毒肽——芋螺马芬在pH 5的溶液结构

黄飞娟, 杜为红, 王保怀   

  1. 中国人民大学化学系, 北京 100872; 北京大学物理化学研究所, 北京 100871
  • 收稿日期:2008-04-08 修回日期:2008-05-16 发布日期:2008-09-10
  • 通讯作者: 杜为红 E-mail:whdu@chem.ruc.edu.cn

Solution Structure of Conomarphin, a Novel Conopeptide Containing D-Amino Acid at pH 5

HUANG Fei-Juan, DU Wei-Hong, WANG Bao-Huai   

  1. Department of Chemistry, Renmin University of China, Beijing 100872, P. R. China; Institute of Physical Chemistry, Peking University, Beijing 100871, P. R. China
  • Received:2008-04-08 Revised:2008-05-16 Published:2008-09-10
  • Contact: DU Wei-Hong E-mail:whdu@chem.ruc.edu.cn

摘要: 从大理石芋螺毒液中分离得到一种新型的含有D型氨基酸, 并属于M超家族的芋螺毒素——芋螺马芬. 应用2D NMR方法测定了芋螺马芬在pH 5条件下的三维结构, 由205个距离约束, 8个二面角约束以及两个氢键约束得到了20个最优结构. 它们骨架原子的均方根偏差为(0.074依0.029) nm. 芋螺马芬在pH 5条件下的二级结构是位于C端的一个短的310螺旋, 同时在Ala6附近呈一个较为松散的环状区域. 将芋螺马芬在pH 5以及pH 3条件下的溶液结构以及表面电荷进行了比较. 尽管芋螺马芬在pH 5条件下的溶液结构与在pH 3条件下的相比, 在C端有一个相似的二级结构单元, 但是整体的骨架结构截然不同, 在pH 5条件下, 芋螺马芬的表面结构从正面看起来像一个“曲臂”. 结构的差异揭示了芋螺马芬对pH相当敏感, 预示着它在体内的活性可能与酸度密切相关.

关键词: 芋螺马芬, 芋螺肽, D-苯丙氨酸, NMR溶液结构, pH敏感

Abstract: Conomarphin, a novel conopeptide containing D-amino acid, was identified from the venom of Conus marmoreus and classified into M-superfamily of conotoxin. In this article, we reported the 3D structure of conomarphin at pH 5 determined using 2D 1H NMR method in aqueous solution. Twenty converged structures of this peptide were obtained based on 205 distance constraints, 8 dihedral angle constraints, and 2 hydrogen bond constraints. The root mean square deviation (RMSD) values of the backbone atoms were (0.074依0.029) nm. The refined structure of conomarphin at pH 5 contained a short 310-helix at C-terminal of the peptide. It was also characterized by a loose loop centered at Ala6. Comparison of structural and electrostatic potential between conomarphin at pH 3 and pH 5 were presented. Although the solution structure of conomarphin at pH 5 shared part of the same secondary structure element with the structure of conomarphin at pH 3, it adopted a distinctive backbone conformation with the overall molecule resembling a“flexcual arm”when viewed fromthe front. Structural differences imply that this conopeptide is rather pH sensitive and its bioactivity in vivo might be related to the acidity.

Key words: Conomarphin, Conopeptide, D-Phenylalanine, NMR solution structure, pH sensitive

MSC2000: 

  • O641