STRUCTURAL STUDIES OF PROTEINS INVOLVED IN THE LPS BIOSYNTHETIC PATHWAY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 内毒素是革兰氏阴性细菌细胞壁的主要成分。脂多糖由三个组分组成：类脂A、核心多糖(Kdo和一个或多个七糖残基)和多糖侧链。在添加庚糖之前停止的内毒素生物合成导致表型深度粗糙，膜对抗生素的通透性增加。因此，庚糖的生物合成途径已被标记为潜在的药物靶点。我们的目标是确定GmhA，一种催化腺苷-L-甘油-甘露七糖生物合成第一步的异构酶，以及GmhB和HldE，这也是脂多糖生物合成的关键因素。确定这些蛋白使用的酶机制将有助于合理设计GmhA、GmhB和HldE抑制剂作为对抗革兰氏阴性感染的手段。

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.