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来自亚马逊蝎子Tityus cambridgei的两种新型毒素,它们以明显不同的亲和力阻断Kv1.3和Shaker B K(+)通道。

Two novel toxins from the Amazonian scorpion Tityus cambridgei that block Kv1.3 and Shaker B K(+)-channels with distinctly different affinities.

作者信息

Batista Cesar V F, Gómez-Lagunas Froylan, Rodríguez de la Vega Ricardo C, Hajdu Péter, Panyi György, Gáspár Rezsõ, Possani Lourival D

机构信息

Department of Molecular Recognition and Structural Biology, Institute of Biotechnology, National Autonomous University of Mexico, Colonia Chamilpa Avenida Universidad, 2001 Cuernavaca 62210, Mexico.

出版信息

Biochim Biophys Acta. 2002 Dec 16;1601(2):123-31. doi: 10.1016/s1570-9639(02)00458-2.

DOI:10.1016/s1570-9639(02)00458-2
PMID:12445473
Abstract

Two novel toxic peptides (Tc30 and Tc32) were isolated and characterized from the venom of the Brazilian scorpion Tityus cambridgei. The first have 37 and the second 35 amino acid residues, with molecular masses of 3,871.8 and 3,521.5, respectively. Both contain three disulfide bridges but share only 27% identity. They are relatively potent inhibitors of K(+)-currents in human T lymphocytes with K(d) values of 10 nM for Tc32 and 16 nM for Tc30, but they are less potent or quite poor blockers of Shaker B K(+)-channels, with respective K(d) values of 74 nM and 4.7 microM. Tc30 has a lysine in position 27 and a tyrosine at position 36 identical to those of charybdotoxin. These two positions conform the dyad considered essential for activity. On the contrary, Tc32 has a serine in the position equivalent to lysine 27 of charybdotoxin and does not contain any aromatic amino acid. Due to its unique primary sequence and to its distinctive preference for K(+)-channels of T lymphocytes, it was classified as the first example of a new subfamily of K(+)-channel-specific peptides (alpha-KT x 18.1). Tc30 is a member of the Tityus toxin II-9 subfamily and was given the number alpha-KT x 4.4.

摘要

从巴西蝎子Tityus cambridgei的毒液中分离并鉴定出两种新型有毒肽(Tc30和Tc32)。第一种有37个氨基酸残基,第二种有35个氨基酸残基,分子量分别为3871.8和3521.5。两者都含有三个二硫键,但序列同源性仅为27%。它们是人类T淋巴细胞中K(+)电流的相对强效抑制剂,Tc32的K(d)值为10 nM,Tc30的K(d)值为16 nM,但它们对Shaker B K(+)通道的抑制作用较弱或很差,各自的K(d)值分别为74 nM和4.7 μM。Tc30在第27位有一个赖氨酸,在第36位有一个酪氨酸,与蝎毒素的相应位置相同。这两个位置构成了被认为对活性至关重要的二元组。相反,Tc32在与蝎毒素第27位赖氨酸等效的位置有一个丝氨酸,并且不含有任何芳香族氨基酸。由于其独特的一级序列以及对T淋巴细胞K(+)通道的独特偏好,它被归类为K(+)通道特异性肽新亚家族(α-KT x 18.1)的首个实例。Tc30是Tityus毒素II-9亚家族的成员,被命名为α-KT x 4.4。

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