近日，英國諾丁漢大學生物分子科學中心研究人員表示,，他們發(fā)現(xiàn)了對付大腸桿菌菌株的新線索。研究結果發(fā)表在了《生物化學期刊》（Journal of Biological Chemistry）上,。
研究人員指明了如何使“細菌素”——能夠殺死其他細菌菌株的物質——進入細菌細胞進而殺死它,，以及如何讓大腸桿菌產生的大腸桿菌素A有針對性地到另一個細胞蛋白（TolA）中創(chuàng)建一個新的“特洛伊木馬”武器，并最終從內部殺死該細菌細胞,。這項研究對于了解分子如何穿透細菌細胞的防御有重要的意義,。
目前，大腸桿菌菌株造成的感染的數量比耐甲氧西林金黃色葡萄球菌和難辨梭菌兩者加起來還多，并且對常規(guī)治療方法的抗藥性越來越強,。因此,，利用細菌的毒性來打擊該細菌將是未來的發(fā)展方向。該新研究探討了大腸桿菌素的物理互動過程,，研究人員發(fā)現(xiàn)大腸桿菌素A與TolA能夠在一個相對面積較小的地區(qū)相互作用,，這個結合區(qū)域強調了分子間的基本互動，并可以保證復雜的相互作用的穩(wěn)定,。研究人員表示,，有足夠的證據表明，大腸桿菌素A和TolA的結合能夠在很大程度上影響細菌細胞的健康,。
該研究領頭人Christopher Penfold表示,，通過這項研究，最終還可能設計出小的新型人工合成化合物,，引導出潛在的抗菌療法,，最終阻止TolA的自然功能來消除細胞的死亡和感染。
但是,，研究者們還發(fā)現(xiàn)即使大腸桿菌素具有良好的抗菌活性，但目前仍然很難將它們作為潛在的新的抗生素被投入使用,。主要因為大腸桿菌素是大的蛋白質分子,，會激活人體的免疫反應，而在下一次的大腸桿菌素被用于治療時會成為抗體,。（生物谷Bioon.com）
doi:10.1074/jbc.M112.342246
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Structural Evidence That Colicin A Protein Binds to a Novel Binding Site of TolA Protein in Escherichia coli Periplasm*
Chan Li?,1,2, Ying Zhang?,1, Mireille Vankemmelbeke?, Oliver Hecht§, Fadilah Sfouq Aleanizy?, Colin Macdonald§, Geoffrey R. Moore§, Richard James? and Christopher N. Penfold?,3
The Tol assembly of proteins is an interacting network of proteins located in the Escherichia coli cell envelope that transduces energy and contributes to cell integrity. TolA is central to this network linking the inner and outer membranes by interactions with TolQ, TolR, TolB, and Pal. Group A colicins, such as ColA, parasitize the Tol network through interactions with TolA and/or TolB to facilitate translocation through the cell envelope to reach their cytotoxic site of action. We have determined the first structure of the C-terminal domain of TolA (TolAIII) bound to an N-terminal ColA polypeptide (TA53–107). The interface region of the TA53–107-TolAIII complex consists of polar contacts linking residues Arg-92 to Arg-96 of ColA with residues Leu-375–Pro-380 of TolA, which constitutes a β-strand addition commonly seen in more promiscuous protein-protein contacts. The interface region also includes three cation-π interactions (Tyr-58–Lys-368, Tyr-90–Lys-379, Phe-94–Lys-396), which have not been observed in any other colicin-Tol protein complex. Mutagenesis of the interface residues of ColA or TolA revealed that the effect on the interaction was cumulative; single mutations of either partner had no effect on ColA activity, whereas mutations of three or more residues significantly reduced ColA activity. Mutagenesis of the aromatic ring component of the cation-π interacting residues showed Tyr-58 of ColA to be essential for the stability of complex formation. TA53–107 binds on the opposite side of TolAIII to that used by g3p, ColN, or TolB, illustrating the flexible nature of TolA as a periplasmic hub protein
