STRUCTURAL STUDIES OF TRYPANOSOMAL GLYCOLYTIC ENZYMES

锥虫糖酵解酶的结构研究

• 批准号: 6586535
• 负责人: HIDONG KIM
• 金额: $ 14.32万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6586535
• 关键词: bioimaging /biomedical imaging; biomaterials; biomedical resource; parasite infection mechanism; proteins; radiography; structural biology

The parasitic trypanosomal species of the genera Trypanosoma and Leishmania are the causative agents of a wide variety of severely destructive diseases. One of the deadliest of these diseases is African sleeping sickness, the causative agent of which is Trypanosoma bruccei. Compounds which selectively inhibit trypanosomal glycolytic enzymes over the equivalent human glycolytic enzymes would be an excellent starting point for the design of new drugs effective in attentuating trypanosomal diseases. We propose to employ a cyclic process of three-dimensional structure determination and molecular modelling in the search for such compounds. This proposal concerns the structural determination aspect of the drug design cycle pertaining to two of these trypanosomal glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and aldolase.

锥虫属的寄生锥虫种和 利什曼原虫是各种严重的病原体， 破坏性疾病。 这些疾病中最致命的一种是 锥虫病一种非洲昏睡病，其病原体是锥虫 布鲁斯。 选择性抑制锥虫糖酵解的化合物 与人类糖酵解酶相比， 这是设计新药的良好起点， 减轻锥虫病。 我们建议采用循环 三维结构测定和分子 在寻找这种化合物的过程中进行建模。 这项建议涉及 药物设计周期的结构决定方面 属于这些锥虫糖酵解酶中的两种， 甘油醛-3-磷酸脱氢酶（GAPDH）和醛缩酶。