Chen Bin, Colgrave Michelle L, Wang Conan, Craik David J
Institute for Molecular Bioscience, Australian Research Council Special Research Centre for Functional and Applied Genomics, University of Queensland, Brisbane, QLD 4072, Australia.
J Nat Prod. 2006 Jan;69(1):23-8. doi: 10.1021/np050317i.
Cycloviolacin H4, a new macrocyclic miniprotein comprising 30 amino acid residues, was isolated from the underground parts of the Australian native violet Viola hederaceae. Its sequence, cyclo-(CAESCVWIPCTVTALLGCSCSNNVCYNGIP), was determined by nanospray tandem mass spectrometry and quantitative amino acid analysis. A knotted disulfide arrangement, which was designated as a cyclic cystine knot motif and characteristic to all known cyclotides, is proposed for stabilizing the molecular structure and folding. The cyclotide is classified in the bracelet subfamily of cyclotides due to the absence of a cis-Pro peptide bond in the circular peptide backbone. A model of its three-dimensional structure was derived based on the template of the homologous cyclotide vhr1 (Trabi et al. Plant Cell 2004, 16, 2204-2216). Cycloviolacin H4 exhibits the most potent hemolytic activity in cyclotides reported so far, and this activity correlates with the size of a surface-exposed hydrophobic patch. This work has thus provided insight into the factors that modulate the cytotoxic properties of cyclotides.
环紫罗兰素H4是一种由30个氨基酸残基组成的新型大环小蛋白，从澳大利亚本土紫罗兰常春藤叶堇菜的地下部分分离得到。其序列为环-(CAESCVWIPCTVTALLGCSCSNNVCYNGIP)，通过纳米喷雾串联质谱和定量氨基酸分析确定。为稳定分子结构和折叠，提出了一种打结的二硫键排列方式，该方式被指定为环胱氨酸结基序，是所有已知环肽的特征。由于环肽主链中不存在顺式脯氨酸肽键，该环肽被归类为环肽的手镯亚家族。基于同源环肽vhr1的模板（特拉比等人，《植物细胞》，2004年，第16卷，第2204 - 2216页）推导了其三维结构模型。环紫罗兰素H4在迄今为止报道的环肽中表现出最强的溶血活性，且这种活性与表面暴露的疏水斑块大小相关。因此，这项工作为调节环肽细胞毒性特性的因素提供了见解。
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