Identification and characterization of novel reptile cathelicidins from elapid snakes
Identification and characterization of novel reptile cathelicidins from elapid snakes
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石蛇中新型爬行动物抗菌肽的鉴定和表征
DOI：
10.1016/j.peptides.2008.06.008
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发表时间：
2008-10-01
期刊：
影响因子：
3
通讯作者：
Zhang, Yun
中科院分区：
文献类型：
--
作者：
Zhao, Hui;Gan, Tong-Xiang;Zhang, Yun
从已构建的眼镜蛇、金环蛇和眼镜蛇毒腺cDNA文库中克隆了3个编码眼镜蛇cathelicidins的cDNA序列。克隆的眼镜蛇cathelicidins开放阅读框均为576 bp，编码191个氨基酸残基的蛋白质前体。推导的眼镜蛇cathelicidin均含有22个氨基酸的信号肽、135个氨基酸的cathelin保守结构域和34个氨基酸的成熟抗菌肽。与哺乳动物中高度分化的cathelicidins不同，三个克隆的眼镜蛇cathelicidins的核苷酸和推导的蛋白质序列非常保守。所有的眼镜蛇成熟cathelicidin被预测为被弹性蛋白酶在缬氨酸157处切割。化学合成了眼镜王蛇Cathelicidin的成熟产物OH-CATH，在1%NaCl存在下，对多种细菌的最小抑菌浓度为1-20 μ g/ml。同时，即使在200 μ g/ml的高剂量下，合成肽对人红细胞也没有溶血活性。系统发育分析表明，蛇类和蝰蛇类cathelicidins在进化树中聚在一起。蛇cathelicidins与小鼠、大鼠和兔的嗜酸性颗粒蛋白（NGPs）在进化上密切相关。蛇类cathelicidins与禽类fowlicidins（1-3）和鸡髓样抗菌肽27也有密切关系。蛇cathelicidins可能被用作开发新的治疗药物的模型。(C)2008年爱思唯尔公司All rights reserved.
Three cDNA sequences coding for elapid cathelicidins were cloned from constructed venom gland cDNA libraries of Naja atra, Bungarus fasciatus and Ophiophagus hannah. The open reading frames of the cloned elapid cathelicidins were all composed of 576 bp and coded for 191 amino acid residue protein precursors. Each of the deduced elapid cathelicidin has a 22 amino acid residue signal peptide, a conserved cathelin domain of 135 amino acid residues and a mature antimicrobial peptide of 34 amino acid residues. Unlike the highly divergent cathelicidins in mammals, the nucleotide and deduced protein sequences of the three cloned elapid cathelicidins were remarkably conserved. All the elapid mature cathelicidins were predicted to be cleaved at Valine157 by elastase. OH-CATH, the deduced mature cathelicidin from king cobra, was chemically synthesized and it showed strong antibacterial activity against various bacteria with minimal inhibitory concentration of 1-20 mu g/ml in the presence of 1% NaCl. Meanwhile, the synthetic peptide showed no haemolytic activity toward human red blood cells even at a high dose of 200 mu g/ml. Phylogenetic analysis of cathelicidins from vertebrate suggested that elapid and viperid cathelicidins were grouped together in the tree. Snake cathelicidins were evolutionary closely related to the neutrophilic granule proteins (NGPs) from mouse, rat and rabbit. Snake cathelicidins also showed a close relationship with avian fowlicidins (1-3) and chicken myeloid antimicrobial peptide 27. Elapid cathelicidins might be used as models for the development of novel therapeutic drugs. (C) 2008 Elsevier Inc. All rights reserved.