Cysteine-Rich Peptide Family with Unusual Disulfide Connectivity from Jasminum sambac
Cysteine-Rich Peptide Family with Unusual Disulfide Connectivity from Jasminum sambac
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DOI：
10.1021/acs.jnatprod.5b00762
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发表时间：
2015-11-01
影响因子：
5.1
通讯作者：
Tam, James P.
中科院分区：
文献类型：
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作者：
Kumari, Geeta;Serra, Aida;Tam, James P.
富含半胱氨酸的肽（Cystine-rich peptides，CRP）是一类具有特殊肽结构的天然产物，是生物活性化合物的潜在丰富来源。在这里，一个新的植物CRP家族，茉莉素从茉莉属的木犀科，发现和表征。在基因和蛋白水平上鉴定了两个由27个氨基酸组成的茉莉素肽（jS 1和jS 2）。通过质谱法对jS 1进行的二硫键作图及其通过NMR光谱法的确认揭示了C-1-C-5、C-2-C-4和C-3-C-6的二硫键连接性，这是一种在植物CRP中尚未报道的胱氨酸基序。结构测定表明，jS 1显示出由三个短的反平行β-折叠构成的明确结构。基因组分析表明，茉莉素肽共享一个三结构域的前体安排与C-末端的成熟结构域之前的46个残基的长pro-domain和信号序列和pro-domain之间的内含子切割位点。紧密的富含半胱氨酸的结构与N-末端焦谷氨酸残基一起赋予jasmintides对热和酶促降解（包括外肽酶处理）的高抗性。总的来说，这些结果揭示了一种新的植物CRP结构与一个不寻常的胱氨酸连接，这可能是有用的设计肽药物的支架。
Cysteine-rich peptides (CRPs) are natural products with privileged peptidyl structures that represent a potentially rich source of bioactive compounds. Here, the discovery and characterization of a novel plant CRP family, jasmintides from Jasminum sambac of the Oleaceae family, are described. Two 27-amino acid jasmintides (jS1 and jS2) were identified at the gene and protein levels. Disulfide bond mapping of jS1 by mass spectrometry and its confirmation by NMR spectroscopy revealed disulfide bond connectivity of C-1-C-5, C-2-C-4, and C-3-C-6, a cystine motif that has not been reported in plant CRPs. Structural determination showed that jS1 displays a well-defined structure framed by three short antiparallel beta-sheets. Genomic analysis showed that jasmintides share a three-domain precursor arrangement with a C-terminal mature domain preceded by a long pro-domain of 46 residues and an intron cleavage site between the signal sequence and pro-domain. The compact cysteine-rich structure together with an N-terminal pyroglutamic acid residue confers jasmintides high resistance to heat and enzymatic degradation, including exopeptidase treatment. Collectively, these results reveal a new plant CRP structure with an unusual cystine connectivity, which could be useful as a scaffold for designing peptide drugs.