(1)Department of Biochemistry and Molecular Biology and Waksman Institute of Microbiology, Rutgers, the State University of New Jersey, Piscataway, NJ 08854, USA.
J Mol Biol. 2011 Oct 7;412(5):842-8. doi: 10.1016/j.jmb.2011.02.060. Epub 2011 Mar 15.
Capistruin, a ribosomally synthesized, post-translationally modified peptide produced by Burkholderia thailandensis E264, efficiently inhibits growth of Burkholderia and closely related Pseudomonas strains. The functional target of capistruin is not known. Capistruin is a threaded-lasso peptide (lariat peptide) consisting of an N-terminal ring of nine amino acids and a C-terminal tail of 10 amino acids threaded through the ring. The structure of capistruin is similar to that of microcin J25 (MccJ25), a threaded-lasso antibacterial peptide that is produced by some strains of Escherichia coli and targets DNA-dependent RNA polymerase (RNAP). Here, we show that capistruin, like MccJ25, inhibits wild type E. coli RNAP but not mutant, MccJ25-resistant, E. coli RNAP. We show further that an E. coli strain resistant to MccJ25, as a result of a mutation in an RNAP subunit gene, exhibits resistance to capistruin. The results indicate that the structural similarity of capistruin and MccJ25 reflects functional similarity and suggest that the functional target of capistruin, and possibly other threaded-lasso peptides, is bacterial RNAP.
泰国伯克霍尔德菌 E264 产生的核糖体合成、翻译后修饰的肽类化合物 Capistruin 能有效抑制伯克霍尔德菌和密切相关的假单胞菌菌株的生长。Capistruin 的功能靶点尚不清楚。Capistruin 是一种穿线套索肽（套索肽），由 9 个氨基酸组成的 N 端环和 10 个氨基酸组成的 C 端尾穿过环。Capistruin 的结构与微菌素 J25（MccJ25）相似，MccJ25 是一种由某些大肠杆菌菌株产生的穿线套索抗菌肽，靶向 DNA 依赖性 RNA 聚合酶（RNAP）。在这里，我们表明 Capistruin 与 MccJ25 一样，抑制野生型大肠杆菌 RNAP，但不抑制 MccJ25 抗性突变大肠杆菌 RNAP。我们进一步表明，由于 RNAP 亚基基因突变，对 MccJ25 产生抗性的大肠杆菌菌株对 Capistruin 表现出抗性。结果表明，Capistruin 和 MccJ25 的结构相似反映了功能的相似性，并表明 Capistruin 的功能靶点，可能还有其他穿线套索肽，是细菌的 RNAP。
