二硫键在氯毒素的结构与活性中的作用。
The role of disulfide bonds in structure and activity of chlorotoxin.
作者信息
Ojeda Paola G, Chan Lai Y, Poth Aaron G, Wang Conan K, Craik David J
机构信息
Institute for Molecular Bioscience, The University of Queensland, Brisbane 4072, QLD, Australia.
出版信息
Future Med Chem. 2014 Oct;6(15):1617-28. doi: 10.4155/fmc.14.93.
BACKGROUND
Chlorotoxin is a small scorpion peptide that inhibits glioma cell migration. We investigated the importance of a major component of chlorotoxin's chemical structure - four disulfide bonds - to its tertiary structure and biological function.
RESULTS
Five disulfide bond analogs of chlorotoxin were synthesized, with l-α-aminobutyric acid residues replacing each or all of the disulfide bonds. Chemical oxidation and circular dichroism experiments revealed that Cys III-VII and Cys V-VIII were essential for native structure formation. Cys I-IV and Cys II-VI were important for stability of enzymatic proteolysis but not for the inhibition of human umbilical vein endothelial cell migration.
CONCLUSION
The disulfide bonds of chlorotoxin are important for its structure and stability and have a minor role in its activity against cell migration.
背景
氯毒素是一种抑制胶质瘤细胞迁移的小蝎子肽。我们研究了氯毒素化学结构的一个主要成分——四个二硫键——对其三级结构和生物学功能的重要性。
结果
合成了氯毒素的五个二硫键类似物，用L-α-氨基丁酸残基取代每个或所有二硫键。化学氧化和圆二色性实验表明，半胱氨酸III-VII和半胱氨酸V-VIII对天然结构形成至关重要。半胱氨酸I-IV和半胱氨酸II-VI对酶促蛋白水解的稳定性很重要，但对抑制人脐静脉内皮细胞迁移不重要。
结论
氯毒素的二硫键对其结构和稳定性很重要，在其抗细胞迁移活性中起次要作用。
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