Bragagnolo Nicholas, Rodriguez Christina, Samari-Kermani Naveed, Fours Alice, Korouzhdehi Mahboubeh, Lysenko Rachel, Audette Gerald F
Department of Chemistry and the Centre for Research on Biomolecular Interactions, York University, Toronto, ON M3J 1P3, Canada.
Department of Chemistry, York University, Toronto, ON M3J 1P3, Canada.
Biomedicines. 2020 Sep 19;8(9):362. doi: 10.3390/biomedicines8090362.
Efficient in silico development of novel antibiotics requires high-resolution, dynamic models of drug targets. As conjugation is considered the prominent contributor to the spread of antibiotic resistance genes, targeted drug design to disrupt vital components of conjugative systems has been proposed to lessen the proliferation of bacterial antibiotic resistance. Advancements in structural imaging techniques of large macromolecular complexes has accelerated the discovery of novel protein-protein interactions in bacterial type IV secretion systems (T4SS). The known structural information regarding the F-like T4SS components and complexes has been summarized in the following review, revealing a complex network of protein-protein interactions involving domains with varying degrees of disorder. Structural predictions were performed to provide insight on the dynamicity of proteins within the F plasmid conjugative system that lack structural information.
新型抗生素的高效计算机模拟开发需要药物靶点的高分辨率动态模型。由于接合作用被认为是抗生素抗性基因传播的主要因素，因此有人提出进行靶向药物设计以破坏接合系统的关键组成部分，从而减少细菌抗生素抗性的扩散。大型大分子复合物结构成像技术的进步加速了细菌IV型分泌系统（T4SS）中新型蛋白质 - 蛋白质相互作用的发现。以下综述总结了有关F样T4SS组件和复合物的已知结构信息，揭示了一个涉及不同程度无序结构域的蛋白质 - 蛋白质相互作用的复杂网络。进行了结构预测，以深入了解缺乏结构信息的F质粒接合系统中蛋白质的动态性。
