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.

摘要

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.