This paper describes the X-ray crystallographic structure of a derivative of the antibiotic teixobactin and shows that its supramolecular assembly through the formation of antiparallel β-sheets creates binding sites for oxyanions. An active derivative of teixobactin containing lysine in place of allo-enduracididine assembles to form amyloid-like fibrils, which are observed through a thioflavin T fluorescence assay and by transmission electron microscopy. A homologue, bearing an N-methyl substituent, to attenuate fibril formation, and an iodine atom, to facilitate X-ray crystallographic phase determination, crystallizes as double helices of β-sheets that bind sulfate anions. β-Sheet dimers are key subunits of these assemblies, with the N-terminal methylammonium group of one monomer and the C-terminal macrocycle of the other monomer binding each anion. These observations suggest a working model for the mechanism of action of teixobactin, in which the antibiotic assembles and the assemblies bind lipid II and related bacterial cell wall precursors on the surface of Gram-positive bacteria.

中文翻译：

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Teixobactin 衍生物的 X 射线晶体结构揭示类淀粉样蛋白组装

本文描述了抗生素 teixobactin 衍生物的 X 射线晶体结构，并表明其通过形成反平行 β-折叠的超分子组装为氧阴离子创造了结合位点。teixobactin 的活性衍生物含有赖氨酸代替异核糖苷酸，组装形成淀粉样原纤维，通过硫代黄素 T 荧光测定和透射电子显微镜观察。带有 N-甲基取代基以减弱原纤维形成的同系物和一个碘原子，以促进 X 射线晶相测定，结晶为结合硫酸根阴离子的双螺旋 β-折叠。β-片二聚体是这些组装的关键亚基，一种单体的 N 端甲基铵基团和另一种单体的 C 端大环结合每个阴离子。这些观察结果表明了 teixobactin 作用机制的工作模型，其中抗生素组装并且组装件结合脂质 II 和革兰氏阳性细菌表面上的相关细菌细胞壁前体。