Characterization and Inhibition of protein-protein interactions involving Staphylococcus aureus GpsB

摘要 GpsB是一种细胞内锚定蛋白，与多种参与细胞分裂的酶相互作用，并 细胞壁合成。全面了解GpsB和ITS之间的蛋白质相互作用 合作伙伴将提供关于肽聚糖合成的调控和各种 细胞生长和分裂过程中的细胞过程，同时为新型抗生素提供了一个有价值的靶点 发展。这项建议的重点是金黄色葡萄球菌，这是一种人类病原体，其GpsB是必不可少的 为其生存，并包含独特的结构特征没有观察到其他同源物。我们的目标是建立 一个多学科平台来表征GpsB与潜在伙伴蛋白(PBP2，FtsZ， Targ)，并鉴定环肽和小分子配体，以研究GpsB的功能和抑制作用。这个 这些结果将为未来深入分析依赖于GpsB的蛋白质复合体奠定基础 潜在的细菌细胞分裂，以及一个发现细胞活性高亲和力的抗生素发现计划 与GpsB结合的化合物。

Abstract GpsB is an intracellular anchor protein that interacts with a multitude of enzymes involved in cell division and cell wall synthesis. Comprehensive understanding of protein-protein interactions between GpsB and its partners will offer crucial information on the regulation of peptidoglycan synthesis and coordination of various cellular processes during cell growth and division, while providing a valuable target for novel antibiotic development. This proposal focuses on Staphylococcus aureus, a human pathogen whose GpsB is essential for its survival and contains unique structural features not observed in other homologs. The goal is to establish a multi-disciplinary platform to characterize GpsB interactions with potential partner proteins (PBP2, FtsZ, TarG), and to identify cyclic peptide and small molecule ligands for studying GpsB function and inhibition. The results will lay the foundation for a future in-depth analysis of the GpsB-dependent protein complexes underlying bacterial cell division, and an antibiotic discovery program to uncover cell-active high affinity compounds binding to GpsB.