Novel Inhibitor Cystine Knot Peptides from Momordica charantia
He, Wen-Jun1; Chan, Lai Yue2; Clark, Richard J.2,3; Tang, Jun1; Zeng, Guang-Zhi1; Franco, Octavio L.4; Cantacessi, Cinzia5; Craik, David J.2; Daly, Norelle L.2,5; Tan, Ning-Hua1
2013-10-08
发表期刊PLOS ONE
ISSN1932-6203
卷号8期号:10页码:e75334
摘要Two new peptides, MCh-1 and MCh-2, along with three known trypsin inhibitors (MCTI-I, MCTI-II and MCTI-III), were isolated from the seeds of the tropical vine Momordica charantia. The sequences of the peptides were determined using mass spectrometry and NMR spectroscopy. Using a strategy involving partial reduction and stepwise alkylation of the peptides, followed by enzymatic digestion and tandem mass spectrometry sequencing, the disulfide connectivity of MCh-1 was elucidated to be CysI-CysIV, CysII-CysV and CysIII-CysVI. The three-dimensional structures of MCh-1 and MCh-2 were determined using NMR spectroscopy and found to contain the inhibitor cystine knot (ICK) motif. The sequences of the novel peptides differ significantly from peptides previously isolated from this plant. Therefore, this study expands the known peptide diversity in M. charantia and the range of sequences that can be accommodated by the ICK motif. Furthermore, we show that a stable two-disulfide intermediate is involved in the oxidative folding of MCh-1. This disulfide intermediate is structurally homologous to the proposed ancestral fold of ICK peptides, and provides a possible pathway for the evolution of this structural motif, which is highly prevalent in nature.
关键词Amino-acid-sequences Trypsin-inhibitor Plasmodium-falciparum Proteinase-inhibitors Cytotoxic Cyclotides Mass-spectrometry Folding Pathways Linn Seeds Kalata B1 X-ray
资助信息National Basic Research Program of China [2013CB127505, 2009CB522300]; National New Drug Innovation Great Project of China [2011ZX09307-002-02]; National Natural Science Foundation of China [21202174, U1032602, 91013002, 30725048]; foundation of Chinese Academy of Sciences (Hundred Talents Program); Natural Science Foundation of Yunnan Province [2012GA003]; China Scholarship Council; Queensland Smart State Fellowship; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior; Fundacao de Apoio a Pesquisa do Distrito Federal
学科领域Multidisciplinary Sciences
收录类别SCI
语种英语
WOS研究方向Science & Technology - Other Topics
WOS类目Multidisciplinary Sciences
WOS记录号WOS:000325552200016
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/17278
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Chinese Acad Sci, State Key Lab Phytochem & Plant Resources West Ch, Kunming Inst Bot, Kunming, Yunnan, Peoples R China
2.Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia
3.Univ Queensland, Sch Biomed Sci, Brisbane, Qld, Australia
4.Univ Catolica Brasilia, Ctr Anal Prote & Bioquim, Programa Posgrad Ciencias Genom & Biotecnol, Brasilia, DF, Brazil
5.James Cook Univ, Ctr Biodiscovery & Mol Dev Therapeut, Cairns, Qld, Australia
推荐引用方式
GB/T 7714
He, Wen-Jun,Chan, Lai Yue,Clark, Richard J.,et al. Novel Inhibitor Cystine Knot Peptides from Momordica charantia[J]. PLOS ONE,2013,8(10):e75334.
APA He, Wen-Jun.,Chan, Lai Yue.,Clark, Richard J..,Tang, Jun.,Zeng, Guang-Zhi.,...&Tan, Ning-Hua.(2013).Novel Inhibitor Cystine Knot Peptides from Momordica charantia.PLOS ONE,8(10),e75334.
MLA He, Wen-Jun,et al."Novel Inhibitor Cystine Knot Peptides from Momordica charantia".PLOS ONE 8.10(2013):e75334.
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