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: 10437907
• 负责人: Jianfeng Cai
• 金额: $ 18.69万
• 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 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10437907
• 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; 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 是一种细胞内锚定蛋白，可与多种参与细胞分裂和生长的酶相互作用。 细胞壁合成。全面了解 GpsB 及其蛋白之间的相互作用 合作伙伴将提供有关肽聚糖合成调节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有价值的靶标 发展。该提案重点关注金黄色葡萄球菌，这是一种人类病原体，其 GpsB 至关重要 其生存并包含其他同系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 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 功能和抑制。这 结果将为未来深入分析 GpsB 依赖性蛋白复合物奠定基础 潜在的细菌细胞分裂，以及揭示细胞活性高亲和力的抗生素发现计划 与 GpsB 结合的化合物。

项目成果

GpsB Coordinates Cell Division and Cell Surface Decoration by Wall Teichoic Acids in Staphylococcus aureus.

• DOI: 10.1128/spectrum.01413-22
• 发表时间: 2022-06-29
• 期刊: MICROBIOLOGY SPECTRUM
• 影响因子: 3.7
• 作者: Hammond, Lauren R.;Sacco, Michael D.;Khan, Sebastian J.;Spanoudis, Catherine;Hough-Neidig, Abigail;Chen, Yu;Eswara, Prahathees J.
• 通讯作者: Eswara, Prahathees J.