含有D型氨基酸的新型毒肽——芋螺马芬在pH5的溶液结构(英文)

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

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2DNMR方法测定了芋螺马芬在pH5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±0.029)nm.芋螺马芬在pH5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pH5以及pH3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pH5条件下的溶液结构与在pH3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pH5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.

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±0.029） nm. The refined structure of conomarphin at pH 5 contained a short 3^10-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 from the front. Structural differences imply that this conopeptide is rather pH sensitive and its bioactivity in vivo might be related to the acidity.