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截短的蜂毒明肽和芋螺毒素中的选择性二硫键形成

Selective disulfide formation in truncated apamin and sarafotoxin.

作者信息

Ramalingam K, Snyder G H

机构信息

Department of Biological Sciences, State University of New York, Buffalo 14260.

出版信息

Biochemistry. 1993 Oct 19;32(41):11155-61. doi: 10.1021/bi00092a027.

DOI:10.1021/bi00092a027
PMID:8218178
Abstract

Apamin and sarafotoxin are small peptide toxins which are 18 and 21 residues long, respectively. They both have cysteines at positions 1, 3, 11, and 15. However, the non-cysteine portions of their sequences and the positions of their disulfides are different. In native apamin, the cysteines form disulfides 1-11 and 3-15, whereas in sarafotoxin they form the 1-15 and 3-11 pairs. Truncated analogs have been synthesized which lack the carboxyl-terminal tails following cysteine-15. When oxidized by glutathione, both truncated sequences retain the ability to selectively populate the disulfide combination observed in the respective full-length parent. This ability is retained in the presence of the denaturing agent 5 M guanidinium chloride. Circular dichroism spectra of the nativelike isomers are nearly identical to those of the parent sequence, and are not affected by heating to 75 degrees C or exposure to 5 M guanidinium chloride. The alpha helix observed in apamin is a consequence of both the disulfide topology and the non-cysteine portions of the sequence. There is not much alpha helix when apamin is forced to adopt the disulfides found in native sarafotoxin or when sarafotoxin is forced to adopt the disulfides found in native apamin.

摘要

蜂毒明肽和芋螺毒素是小肽毒素,分别由18个和21个氨基酸残基组成。它们在第1、3、11和15位都有半胱氨酸。然而,它们序列中的非半胱氨酸部分以及二硫键的位置不同。在天然蜂毒明肽中,半胱氨酸形成1-11和3-15二硫键,而在芋螺毒素中,它们形成1-15和3-11二硫键对。已经合成了在半胱氨酸-15之后缺少羧基末端尾巴的截短类似物。当被谷胱甘肽氧化时,两个截短序列都保留了选择性形成各自全长亲本中观察到的二硫键组合的能力。在变性剂5 M氯化胍存在的情况下,这种能力得以保留。类天然异构体的圆二色光谱与亲本序列的光谱几乎相同,并且不受加热至75摄氏度或暴露于5 M氯化胍的影响。在蜂毒明肽中观察到的α螺旋是二硫键拓扑结构和序列中非半胱氨酸部分共同作用的结果。当蜂毒明肽被迫采用天然芋螺毒素中的二硫键时,或者当芋螺毒素被迫采用天然蜂毒明肽中的二硫键时,α螺旋不多。

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