Mechanically interlocked molecules that change their conformation in response to stimuli have been developed by synthetic chemists as building blocks for molecular machines. Here we describe a natural product, the lasso peptide benenodin-1, which exhibits conformational switching between two distinct threaded conformers upon actuation by heat. We have determined the structures of both conformers and have characterized the kinetics and energetics of the conformational switch. Single amino acid substitutions to benenodin-1 generate peptides that are biased to a single conformer, showing that the switching behavior is potentially an evolvable trait in these peptides. Lasso peptides such as benenodin-1 can be recognized and cleaved by enzymes called lasso peptide isopeptidases. We show that only the native conformer of benenodin-1 is cleaved by its cognate isopeptidase. Thus, thermally induced conformational switching of benenodin-1 may also be relevant to the biological function of these molecules.

中文翻译：

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套索肽Benenodin-1是一种热驱动[1] Rotaxane开关

合成化学家已经开发出可以响应刺激而改变其构象的机械互锁分子，作为分子机器的基础。在这里，我们描述了一种天然产物，套索肽benonodin-1，它在受热致动后在两个不同的螺纹构象异构体之间显示构象转换。我们已经确定了两个构象异构体的结构，并表征了构象转换的动力学和能量学。苯甲菌素-1的单个氨基酸取代产生偏向单个构象异构体的肽，表明转换行为可能是这些肽中可进化的性状。套索肽（例如benonodin-1）可以被称为套索肽异肽酶的酶识别和切割。我们显示，只有benenodin-1的天然构象异构体被其同源异肽酶切割。因此，热诱导的苯那丁-1的构象转换也可能与这些分子的生物学功能有关。