Juan H F, Hung C C, Wang K T, Chiou S H
Institute of Biochemical Sciences, National Taiwan University.
Biochem Biophys Res Commun. 1999 Apr 13;257(2):500-10. doi: 10.1006/bbrc.1999.0437.
We present a systematic structure comparison of three major classes of postsynaptic snake toxins, which include short and long chain alpha-type neurotoxins plus one angusticeps-type toxin of black mamba snake family. Two novel alpha-type neurotoxins isolated from Taiwan cobra (Naja naja atra) possessing distinct primary sequences and different postsynaptic neurotoxicities were taken as exemplars for short and long chain neurotoxins and compared with the major lethal short-chain neurotoxin in the same venom, i.e., cobrotoxin, based on the derived three-dimensional structure of this toxin in solution by NMR spectroscopy. A structure comparison among these two alpha-neurotoxins and angusticeps-type toxin (denoted as FS2) was carried out by the secondary-structure prediction together with computer homology-modeling based on multiple sequence alignment of their primary sequences and established NMR structures of cobrotoxin and FS2. It is of interest to find that upon pairwise superpositions of these modeled three-dimensional polypeptide chains, distinct differences in the overall peptide flexibility and interior microenvironment between these toxins can be detected along the three constituting polypeptide loops, which may reflect some intrinsic differences in the surface hydrophobicity of several hydrophobic peptide segments present on the surface loops of these toxin molecules as revealed by hydropathy profiles. Construction of a phylogenetic tree for these structurally related and functionally distinct toxins corroborates that all long and short toxins present in diverse snake families are evolutionarily related to each other, supposedly derived from an ancestral polypeptide by gene duplication and subsequent mutational substitutions leading to divergence of multiple three-loop toxin peptides.
我们展示了三种主要类型的突触后蛇毒素的系统结构比较，其中包括短链和长链α型神经毒素以及黑曼巴蛇科的一种安古斯蒂塞普斯型毒素。从台湾眼镜蛇（Naja naja atra）中分离出的两种具有不同一级序列和不同突触后神经毒性的新型α型神经毒素被用作短链和长链神经毒素的示例，并基于通过核磁共振光谱法在溶液中获得的该毒素的三维结构，与同一毒液中的主要致死性短链神经毒素，即眼镜蛇毒素进行比较。通过二级结构预测以及基于它们的一级序列的多序列比对以及已建立的眼镜蛇毒素和FS2的核磁共振结构的计算机同源建模，对这两种α神经毒素和安古斯蒂塞普斯型毒素（表示为FS2）进行了结构比较。有趣的是，在对这些模拟的三维多肽链进行两两叠加时，可以沿着三个构成多肽环检测到这些毒素之间在整体肽柔韧性和内部微环境方面的明显差异，这可能反映了这些毒素分子表面环上存在的几个疏水肽段的表面疏水性的一些内在差异，如亲水性图谱所示。为这些结构相关且功能不同的毒素构建系统发育树证实，存在于不同蛇科中的所有长链和短链毒素在进化上彼此相关，推测是由一个祖先多肽通过基因复制以及随后的突变取代导致多个三环毒素肽的分化而来。
