GLUTAMINE SYNTHETASE FROM MYCOBACTERIUM TB, PROTEGRIN & D-LACTATE DEHYDROGEN

结核病重新成为一个全球健康问题，原因是 抗分枝杆菌耐药菌株上升。小说的发现 药物靶标由于需要穿透厚厚的 分枝杆菌的细胞膜。然而，就在最近， 发现结核分枝杆菌分泌谷氨酰胺 合成酶进入其直接环境(Harth等人)。1994)，并且 抑制这种分泌的酶会扰乱正常发育 (未发布数据)。确定中介绍的结构模型 这项提案将作为药物设计的起点。 结合并抑制其作用，从而提供新的治疗方法 与这种疾病作斗争。普罗吉林是一种非常有效的抗生素 多肽，既是抗菌剂又是抗病毒剂。 鉴于前列环素的体积较小，结构相对简单，它 提供了一个有吸引力的模板，用于设计可能有用的 化学保护性多肽。然而，抗菌剂的方法 多肽区分不同的细胞类型，最终摧毁一个 人们对入侵细胞知之甚少。通过将特定的 晶格中蛋白质单体之间的相互作用，我们 将深入了解可能的作用机制 用来治疗前列环素。乳酸脱氢酶(D-LDH)是一种 膜相关呼吸酶。它提供了不同寻常的 研究结构和结构之间关系的机会 在外周膜蛋白中起作用。确定 D-乳酸脱氢酶的三维结构有助于理解 蛋白质-蛋白质和蛋白质-脂质相互作用 了解外周细胞膜蛋白。

Tuberculosis has re-emerged as a global health concern due to a rise in anti-Mycobacterial drug-resistant strains. Discovery of novel drug targets are complicated by the need to penetrate the thick cellular envelop of Mycobacteria. However, it has been recently discovered that Mycobacterium tuberculosis secretes Glutamine Synthetase into its immediate environment (Harth et al. 1994) and that inhibition of this secreted enzyme disrupts normal development (unpublished data). Determining the structural models described in this proposal will serve as a starting point for the design of drugs that bind to and inhibit its action, hence providing new therapies to combat this disease. Protegrin is a remarkably potent antibiotic peptide, effective as both an antimicrobial and an antiviral agent. Given the small size and relatively simple structure of protegrin, it provides an attractive template for designing potentially useful chemoprotective peptides. However, the methods by which antimicrobial peptides discriminate between cell types, and ultimately destroy an invading cell is poorly understood. By characterizing specific interactions between protegrin monomers in the crystal lattice, we will gain insight into understand the possible mechanisms of action for protegrin. D-lactate dehydrogenase (D-LDH) is a membrane-associated respiratory enzyme. It provides unusual opportunity for studying the relationship between structure and function in a peripheral membrane protein. Determining the three-dimensional structure of D-LDH will help understanding the protein-protein and protein-lipid interactions in, the poorly understood peripheral membrane proteins.