NisC Binds the FxLx Motif of the Nisin Leader Peptide
NisC Binds the FxLx Motif of the Nisin Leader Peptide
复制标题
DOI：
10.1021/bi4008116
复制
发表时间：
2013-08-13
期刊：
影响因子：
2.9
通讯作者：
Schmitt, Lutz
中科院分区：
文献类型：
--
作者：
Abts, Andre;Montalban-Lopez, Manuel;Schmitt, Lutz
乳链菌肽是羊毛硫抗生素的模型系统，羊毛硫抗生素是一类对各种革兰氏阳性细菌具有抗菌活性的肽。核糖体合成后，前体肽分两步进行修饰，其中最后一步涉及由环化酶 NisC 介导的连续环化反应。在这里，我们对 NisC 和乳链菌肽前体肽之间的相互作用进行了详细的体外研究。我们的结果揭示了 NisC 与前导肽的特定相互作用，与成熟状态无关。此外，诱变研究确定了前导序列内的特定结合序列。 I 类羊毛硫抗生素高度保守的 -FNLD- 盒内的两个氨基酸（F-18 和 L-16）对于结合至关重要。它们代表了一组羊毛硫抗生素的前导肽与其环化酶家族之间的潜在通用结合基序。总之，这些体外数据为羊毛硫抗生素修饰机制的复杂性提供了新的认识。
Nisin is a model system for lantibiotics, a class of peptides displaying antimicrobial activity against various Gram-positive bacteria. After ribosomal synthesis, the precursor peptide is modified in two steps, of which the last one involves consecutive cyclization reactions mediated by the cyclase NisC. Here, we present a detailed in vitro study of the interaction between NisC and the nisin precursor peptide. Our results unravel a specific interaction of NisC with the leader peptide independent of the maturation state. Furthermore, mutagenesis studies identified a specific binding sequence within the leader. Two amino acids (F-18 and L-16) within the highly conserved -FNLD- box of class I lantibiotics are essential for binding. They represent a potential general binding motif between leader peptides of a group of lantibiotics with their cyclase family. In summary, these in vitro data provide a new perception on the complexity of the lantibiotic modification machineries.