Yamamoto H, Sejbal J, York E, Stewart J M, Possani L D, Kotovych G
Department of Chemistry, University of Alberta, Edmonton, Canada.
Biopolymers. 1999 Apr;49(4):277-86. doi: 10.1002/(SICI)1097-0282(19990405)49:4<277::AID-BIP2>3.0.CO;2-Y.
The solution structure of a synthetic peptide, Cn2(1-15)NH2-S-S-acetyl-Cn2(52-66)NH2 from toxin 2 (Cn2) of the New World scorpion Centruroides noxius was determined using nmr and molecular dynamics calculations. The peptide has no significant secondary structure such as an alpha-helix or a beta-sheet, yet it has a fixed conformation for the first chain. The backbone secondary structure involving residues 6-12 in this peptide shows an excellent overlap with the structures of natural neurotoxins from Centruroides sculpturatus Ewing. Residues 6-9 form a distorted type I beta-turn and residues 10-12 form a gamma-turn. As residues 7-10 in the Centruroides toxins correspond to one of the regions of highest sequence variability, it may account for the species specificity and/or selectivity of toxic action. The conformation of this region evidently plays an important role in receptor recognition and in binding to the neutralizing monoclonal antibody BCF2 raised against the intact toxin.
利用核磁共振(NMR)和分子动力学计算确定了来自新大陆蝎子Centruroides noxius毒素2(Cn2)的合成肽Cn2(1 - 15)NH2 - S - S - 乙酰基 - Cn2(52 - 66)NH2的溶液结构。该肽没有明显的二级结构,如α - 螺旋或β - 折叠,但第一条链具有固定的构象。此肽中涉及6 - 12位残基的主链二级结构与来自Centruroides sculpturatus Ewing的天然神经毒素结构有很好的重叠。6 - 9位残基形成一个扭曲的I型β - 转角,10 - 12位残基形成一个γ - 转角。由于Centruroides毒素中的7 - 10位残基对应于序列变异性最高的区域之一,它可能解释了毒性作用的物种特异性和/或选择性。该区域的构象显然在受体识别以及与针对完整毒素产生的中和单克隆抗体BCF2的结合中起重要作用。