Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, and Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia.
Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, and Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia.
J Struct Biol. 2018 Dec;204(3):396-405. doi: 10.1016/j.jsb.2018.10.008. Epub 2018 Oct 23.
Bacterial sliding clamps bind to DNA and act as protein-protein interaction hubs for several proteins involved in DNA replication and repair. The partner proteins all bind to a common pocket on sliding clamps via conserved linear peptide sequence motifs, which suggest the pocket as an attractive target for development of new antibiotics. Herein we report the X-ray crystal structures and biochemical characterization of β sliding clamps from the Gram-negative pathogens Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacter cloacae. The structures reveal close similarity between the pathogen and Escherichia coli clamps and similar patterns of binding to linear clamp-binding motif peptides. The results suggest that linear motif-sliding clamp interactions are well conserved and an antibiotic targeting the sliding clamp should have broad-spectrum activity against Gram-negative pathogens.
细菌滑动夹与 DNA 结合，并作为涉及 DNA 复制和修复的几种蛋白质的蛋白质-蛋白质相互作用中心。这些伴侣蛋白都通过保守的线性肽序列基序结合到滑动夹的一个共同口袋上，这表明口袋是开发新型抗生素的有吸引力的目标。本文报告了革兰氏阴性病原体铜绿假单胞菌、鲍曼不动杆菌和阴沟肠杆菌的 β 滑动夹的 X 射线晶体结构和生化特性。这些结构揭示了病原体与大肠杆菌夹之间的紧密相似性，以及与线性夹结合基序肽的相似结合模式。结果表明，线性基序-滑动夹相互作用得到了很好的保守，针对滑动夹的抗生素应该对革兰氏阴性病原体具有广谱活性。
