Therostasin, a novel clotting factor Xa inhibitor from the rhynchobdellid leech, Theromyzon tessulatum
Therostasin, a novel clotting factor Xa inhibitor from the rhynchobdellid leech, Theromyzon tessulatum
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DOI：
10.1074/jbc.m909217199
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发表时间：
2000-10-20
影响因子：
4.8
通讯作者：
Malecha, J
中科院分区：
文献类型：
--
作者：
Chopin, V;Salzet, M;Malecha, J
Therostasin是一种有效的天然存在的哺乳动物Xa因子（K-i, 34 pM）紧密结合抑制剂，从rhynchobdellid水蛭Theromyzon tessulatum中分离出来，Therostasin是一种富含半胱氨酸的蛋白（8991 Dal），由82个氨基酸残基和16个半胱氨酸残基组成。其氨基酸序列已通过多种技术确定，包括Edman降解、酶解理和基质辅助激光脱附/电离飞行时间质谱（MALDI-TOF MS）对天然和s- β -吡啶乙基化化合物。序列分析显示，除了推定的活性位点外，它与其他因子Xa抑制剂没有显著的同源性。此外，它含有内皮素家族蛋白的特征模式，从哺乳动物和蛇毒中分离出有效的血管收缩剂。Therostasin cDNA （825bp）编码一个由82个氨基酸残基和19个残基组成的多肽，代表一个信号肽序列。至于其他已知的Xa因子抑制剂，热抑素在水蛭唾液腺细胞中表达和储存。
Therostasin is a potent naturally occurring tight-binding inhibitor of mammalian Factor Xa (K-i, 34 pM), isolated from the rhynchobdellid leech Theromyzon tessulatum, Therostasin is a cysteine-rich protein (8991 Dal consisting of 82 amino acid residues with 16 cysteine residues. Its amino acid sequence has been determined by a combination of techniques, including Edman degradation, enzymatic cleavage, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) on the native and s-beta -pyridylethylated compound. Sequence analysis reveals that it shares no significant homology with other Factor Xa inhibitors except for the putative reactive site. Moreover, it contains a signature pattern for proteins of the endothelin family, potent vasoconstrictors isolated in mammal and snake venom. Therostasin cDNA (825 bp) codes for a polypeptide of 82 amino acid residues preceded by 19 residues, representing a signal peptide sequence. As for the other known inhibitors of Factor Xa, therostasin is expressed and stored in the cells of the leech salivary glands.