New targets for antibiotics: self assembling ribonucleoprotein complexes

抗生素的新靶点：自组装核糖核蛋白复合物

• 批准号: 7914043
• 负责人: LOIS POLLACK
• 金额: $ 26.7万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-10 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7914043
• 关键词: Antibiotic Resistance; Antibiotics; Bacteria; Biological; Complex; Development; Generations; Goals; Growth; Health; Human; Knowledge; Measures; Methods; Molecular Machines; Pathway interactions; Protein Precursors; Proteins; RNA; Ribonucleoproteins; Ribosomes; Time; Work; drug resistant bacteria; fight against; insight; novel strategies; prevent; public health relevance; resistant strain; self assembly; weapons

DESCRIPTION (provided by applicant): Ribosomes are molecular machines that carry out an essential biological task: they synthesize proteins. Thus, bacterial ribosomes are logical targets for antibiotics. However, the emergence (and growth of) drug resistant bacteria poses a major threat to human health. New strategies for attacking resistant strains must be developed. Recent, breakthrough structural studies of the ribosome enable an entirely new approach to interfering with the ribosome: preventing its self assembly. Here, we propose to develop and apply a new experimental method for measuring structural changes accompanying the real time self-assembly of the ribosome or its subunits. If successful, this approach will enable identification of folding pathways or partially folded states that may be amenable to attack. PUBLIC HEALTH RELEVANCE: Large molecular machines, like the ribosome, are constructed from both RNA and protein precursors. The methods we propose will provide unique insight into self-assembly of large ribonucleoprotein complexes, like the ribosome. A long term goal of this work is to guide development of a new generation of antibiotics that interfere with self-assembly. If the approach is successful, this knowledge brings an additional weapon to the fight against antibiotic resistant bacteria, an escalating threat to human health.

描述（由申请人提供）：核糖体是执行基本生物学任务的分子机器：它们合成蛋白质。因此，细菌核糖体是抗生素的逻辑靶标。但是，耐药细菌的出现（和生长）对人类健康构成了主要威胁。必须制定攻击抗性菌株的新策略。核糖体的最新突破性结构研究为干扰核糖体的全新方法：防止其自组装。在这里，我们建议开发和应用一种新的实验方法，用于测量核糖体或其亚基实时自组装的结构变化。如果成功，此方法将能够识别折叠途径或可能适合攻击的部分折叠状态。公共卫生相关性：大分子机器（如核糖体）都是由RNA和蛋白质前体构建的。我们提出的方法将为大型核糖核蛋白复合物（如核糖体）的自组装提供独特的见解。这项工作的长期目标是指导开发新一代的抗生素，这些抗生素会干扰自组装。如果该方法成功，则这种知识为抵抗抗生素耐药细菌的斗争带来了额外的武器，这是对人类健康的不断升级的威胁。