Hadrurin, a new antimicrobial peptide from the venom of the scorpion Hadrurus aztecus
Hadrurin, a new antimicrobial peptide from the venom of the scorpion Hadrurus aztecus
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DOI：
10.1046/j.1432-1327.2000.01556.x
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发表时间：
2000-08-01
期刊：
影响因子：
--
通讯作者：
Possani, LD
中科院分区：
文献类型：
--
作者：
Torres-Larios, A;Gurrola, GB;Possani, LD
采用SephadexG-50凝胶过滤和高效液相色谱法，从墨西哥蝎（Hadrurusaztecus）毒中分离得到一种新的抗菌肽--Hadrurin。它是由41个氨基酸残基组成的碱性肽，分子量为4436 Da，不含半胱氨酸。一个模型的hadrurin的三维折叠是兼容的两亲分子与两个或-螺旋段。Hadrurin在低微摩尔浓度下表现出抗微生物活性，抑制细菌的生长，例如：沙门氏菌、肺炎克雷伯氏菌、阴沟肠球菌、铜绿假单胞菌、大肠杆菌和粘质沙雷氏菌。在人红细胞中检测时，也显示出细胞溶解活性。化学合成Hadrurin和两种类似物（C-末端酰胺化，和所有D-对映异构体）。通过测试其分散不同组成脂质体的扩散电位的能力，将其用于研究可能的分子作用机制。所获得的结果表明，没有特定的受体分子的作用hadrurin，最可能的机制是通过膜去稳定化活动。据推测，Hadrurin被蝎子用作攻击和防御其猎物和假定的入侵微生物的元素。在所有已知的抗菌肽中，它是一种独特的肽，仅部分类似于从青蛙皮肤中分离的gaegurin 4和brevinin 2 e的N-末端片段。它肯定会成为研究新的抗生素活性和肽-脂质相互作用的模型分子。
A new antimicrobial peptide, hadrurin, was isolated from the venom of the Mexican scorpion Hadrurus aztecus, by gel filtration on a Sephadex G-50 column, followed by high performance liquid chromatography. It is a basic peptide composed of 41 amino-acid residues with a molecular mass of 4436 Da, and contains no cysteines. A model of the three-dimensional folding of hadrurin is compatible with that of an amphipatic molecule with two or-helical segments. Hadrurin demonstrates antimicrobial activity at low micromolar concentration, inhibiting the growth of bacteria such as: Salmonella thyphi, Klebsiella pneumoniae, Enterococcus cloacae, Pseudomonas aeruginosa, Escherichia coli and Serratia marscences. It also shows cytolytic activity when tested in human erythrocytes. Hadrurin and two analogs (C-terminal amidated, and all D-enantiomer) were chemically synthesized. They were used to study the possible molecular mechanism of action by testing their ability to dissipate the diffusion potential of liposomes of different compositions. The results obtained indicate that there are no specific receptor molecules for the action of hadrurin, and the most probable mechanism is through a membrane destabilization activity. It is surmised that hadrurin is used by the scorpion as both an attack and defense element against its prey and putative invasive microorganisms. It is a unique peptide among all known antimicrobial peptides described, only partially similar to the N-terminal segment of gaegurin 4 and brevinin 2e, isolated from frog skin. It would certainly be a model molecule for studying new antibiotic activities and peptide-lipid interactions.