Plan Manuel Rey R, Göransson Ulf, Clark Richard J, Daly Norelle L, Colgrave Michelle L, Craik David J
Institute for Molecular Bioscience, Australian Research Council, Special Research Centre for Functional and Applied Genomics, The University of Queensland, Brisbane QLD 4072, Australia.
Chembiochem. 2007 Jun 18;8(9):1001-11. doi: 10.1002/cbic.200700097.
The complete suite of cyclotides present in Oldenlandia affinis (Rubiaceae), the plant that was originally found to contain this unique family of circular proteins, has been characterised. This study expands the number of known cyclotides in this plant to 17, of which nine new sequences (kalata B9-B17) were characterised in this work. In addition, five derivatives that contain oxidation products of the conserved tryptophan were identified, and it was shown that the formation of these derivatives is catalysed by exposure to sunlight. Furthermore, we describe two "linear" cyclotide analogues. These acyclic peptides have three intact disulfide bonds, and their N and C termini coincide with the hypothesised cleavage sites from the precursor protein. This work increases our knowledge about the sequence variation that is accommodated by the cyclic cystine knot scaffold, confirms its applicability as a template for drug design, and also shows the first natural degradation pathways for cyclotides. These pathways have important implications for the persistence and environmental fate of the cyclotides if used as crop-protection agents.
最初发现含有这种独特环状蛋白家族的植物——耳草（茜草科）中存在的完整环肽组已得到表征。这项研究将该植物中已知环肽的数量增加到了17种，其中9个新序列（kalata B9 - B17）在本研究中得到了表征。此外，还鉴定出了5种含有保守色氨酸氧化产物的衍生物，并且表明这些衍生物的形成是由阳光照射催化的。此外，我们还描述了两种“线性”环肽类似物。这些无环肽具有三个完整的二硫键，其N端和C端与前体蛋白的假设切割位点一致。这项工作增加了我们对环状胱氨酸结支架所能容纳的序列变异的了解，证实了其作为药物设计模板的适用性，并且还展示了环肽的首个自然降解途径。如果用作作物保护剂，这些途径对环肽的持久性和环境归宿具有重要意义。
