STRUCTURAL STUDIES OF PROTEINS INVOLVED IN THE LPS BIOSYNTHETIC PATHWAY

LPS 生物合成途径相关蛋白质的结构研究

• 批准号: 7726202
• 负责人: MURRAY JUNOP
• 金额: $ 1.34万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-18 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7726202
• 关键词: Anabolism; Antibiotics; Cell Membrane Permeability; Cell Wall; Commit; Computer Retrieval of Information on Scientific Projects Database; Depth; Drug Delivery Systems; Funding; Goals; Grant; Heptoses; Infection; Institution; Isomerase; Lipid A; Lipopolysaccharide Biosynthesis Pathway; Lipopolysaccharides; Pathway interactions; Phenotype; Polysaccharides; Proteins; Research; Research Personnel; Resources; Side; Source; United States National Institutes of Health; design; inhibitor/antagonist

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lipopolysaccharide (LPS) is a major component of the Gram-negative bacterial cell wall. LPS is comprised of three components: lipid A, core polysaccharide (Kdo and one or more heptose residues), and polysaccharide side chains. LPS biosynthesis that is halted prior to heptose addition results in a deep-rough phenotype and membrane permeability to antibiotics is increased. For this reason, the heptose biosynthetic pathway has been marked as a potential drug target. Our goal is to determine the mechanism of GmhA, an isomerase that catalyzes the first committed step of ADP-L-glycero-¿¿¿x-manno-heptose biosynthesis as well as GmhB and HldE which are also key players in LPS biosynthesis. Determination of the enzymatic mechanisms used by these proteins will aid in the rational design of inhibitors of GmhA, GmhB and HldE as a means to combat Gram negative infection.

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