Cycloviolacin H4, a hydrophobic cyclotide from Viola hederaceae

Cycloviolacin H4, a hydrophobic cyclotide from Viola hederaceae
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DOI:
10.1021/np050317i
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发表时间:
2006-01-01
影响因子:
5.1
通讯作者:
Craik, DJ
Craik, DJ
中科院分区:
生物学2区
文献类型:
--
作者:
Chen, B;Colurave, ML;Craik, DJ

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Cycloviolacin H4 是一种新的大环小蛋白,包含 30 个氨基酸残基,是从澳大利亚本土紫罗兰常春藤的地下部分分离出来的。通过纳喷雾串联质谱和定量氨基酸分析确定其环-(CAESVWIPCTVTALLGCSCSNNVCYNGIP) 序列。提出了一种打结的二硫键排列,其被指定为环状胱氨酸结基序并且是所有已知环肽的特征,用于稳定分子结构和折叠。由于环状肽主链中不存在顺式-Pro肽键,环肽被归类为环肽手链亚家族。其三维结构模型是基于同源环肽vhr1的模板推导的(Trabi等人,Plant Cell 2004, 16, 2204-2216)。环紫星 H4 在迄今为止报道的环肽中表现出最有效的溶血活性,并且该活性与表面暴露的疏水斑块的大小相关。因此,这项工作深入了解了调节环肽细胞毒性特性的因素。
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 disuffide 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.