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

金黄色葡萄球菌 GpsB 蛋白-蛋白相互作用的表征和抑制

• 批准号: 10317549
• 负责人: Jianfeng Cai
• 金额: $ 22.43万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-25 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10317549
• 关键词: Adaptor Signaling Protein; Affinity; Antibiotics; Arginine; Bacillus subtilis; Binding; Binding Proteins; Biological; Biological Assay; Biophysics; Cell Membrane Permeability; Cell Shape; Cell Wall; Cell division; Cell physiology; Cells; Crystallization; Custom; Cyclic Peptides; Development; Docking; Engineering; Enzymes; Exhibits; Foundations; Future; Goals; Hot Spot; Lead; Ligands; Membrane; Metabolic; Methods; Microbiology; Molecular; Molecular Conformation; N-terminal; Normal Cell; Organism; Penicillin-Binding Proteins; Peptides; Peptidoglycan; Pharmaceutical Chemistry; Pilot Projects; Play; Protein Inhibition; Proteins; Protomer; Regulation; Research Personnel; Roentgen Rays; Role; Set protein; Side; Staphylococcus aureus; Structure; Surface; Surface Plasmon Resonance; Teichoic Acids; X-Ray Crystallography; analog; bacterial resistance; base; cell growth; dimer; experimental study; functional group; high throughput screening; human pathogen; inhibitor/antagonist; innovation; interdisciplinary approach; multidisciplinary; novel; programs; protein complex; protein protein interaction; small molecule; small molecule inhibitor; virtual screening

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.

抽象的 GPSB是一种细胞内锚固蛋白，与参与细胞分裂的多种酶相互作用， 细胞壁合成。对GPSB及其ITS蛋白质 - 蛋白质相互作用的全面了解 合作伙伴将提供有关调节肽聚糖合成和各种协调的重要信息 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宝贵的靶标 发展。该提案重点是金黄色葡萄球菌，一种人类病原体，其GPSB是必不可少的 因为它的生存并包含在其他同源物中未观察到的独特结构特征。目标是建立 一个多学科平台，用于表征与潜在合作伙伴蛋白的GPSB相互作用（PBP2，FTSZ， targ），并鉴定循环肽和小分子配体用于研究GPSB功能和抑制作用。这 结果将为对GPSB依赖性蛋白质复合物的未来深入分析奠定基础 潜在的细菌细胞分裂和一个抗生素发现程序，以发现细胞活性高亲和力 化合物与GPSB结合。