Zimmermann Marcel, Hegemann Julian D, Xie Xiulan, Marahiel Mohamed A
Department of Chemistry, Biochemistry, Philipps-University Marburg, Marburg, Germany.
Chem Biol. 2013 Apr 18;20(4):558-69. doi: 10.1016/j.chembiol.2013.03.013.
Lasso peptides are a large family of natural products that owe their name to a unique structure formed by a side chain to backbone macrocyclization, resembling a knotted lasso. The unique structure has significant impact on their biological and physical properties, as lasso peptides are usually more stable than linear ones. Current work examines stability, structure, and biosynthesis of recently discovered lasso peptide astexin-1, a heat-sensitive lasso peptide. The obtained results revealed a new lasso structure with a tight loop and long tail as well as narrow specificity of the maturation machinery for some essential residues associated with the protease processing site, involved in macrolactam ring formation and entrapment of the tail. Using the astexin-1 structure, it was possible to rationally construct a thermostable variant of this lasso peptide.
套索肽是一大类天然产物，因其独特的结构而得名，该结构由侧链与主链大环化形成，形似打结的套索。这种独特结构对其生物学和物理性质有重大影响，因为套索肽通常比线性肽更稳定。目前的研究工作考察了最近发现的对热敏感的套索肽阿斯泰辛-1的稳定性、结构和生物合成。所获得的结果揭示了一种具有紧密环和长尾巴的新套索结构，以及成熟机制对与蛋白酶加工位点相关的一些必需残基的狭窄特异性，这些残基参与大环内酰胺环的形成和尾巴的捕获。利用阿斯泰辛-1的结构，有可能合理构建这种套索肽的热稳定变体。
