UNKNOWN

未知

• 批准号: 8170656
• 负责人: ALEXANDER A SERGANOV
• 金额: $ 1.1万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170656
• 关键词: Amino Acids; Antibiotics; Bacteria; Binding; Chemicals; Coenzymes; Complex; Computer Retrieval of Information on Scientific Projects Database; Crystallography; Cues; DNA Sequence Rearrangement; Funding; Gene Expression; Genes; Grant; Institution; Life; Ligands; Messenger RNA; Molecular; Organism; Proteins; Research; Research Personnel; Resources; Source; Structure; System; United States National Institutes of Health; design; novel; response; selective expression; sugar; three dimensional structure

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. All living beings express those genes whose products are needed most at the given moment. To save resources and provide high adaptability to environmental conditions, organisms developed different systems to sense various physical and chemical cues and transmit them to the machinery that provides selective expression of genes. Though typically the sensing function is performed by proteins, recently discovered regulatory circuits involve mRNA regions, termed riboswitches, capable of direct and specific binding of cellular metabolites. Riboswitches are present in all kingdoms of life, and highly abundant in bacteria, including pathogenic species, where they direct expression of many vital genes in response to various metabolites, including coenzymes, amino acids, sugars, and nucleobases. Each riboswitch is folded into an evolutionary conserved three-dimensional structure stabilized by the interaction with the cognate metabolite. Since riboswitches modulate gene expression through conformational rearrangements in their structures, we have focused our research on the determination of the three-dimensional structures of the riboswitch-ligand complexes. The structures will uncover the molecular principles of riboswitch-controlled gene expression and may help in the rational design of novel classes of metabolite-like antibiotics.

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。 所有生物都表达了在特定时刻最需要其产品的基因。为了节约资源并提供对环境条件的高度适应性，生物体开发了不同的系统来感知各种物理和化学线索，并将它们传输到提供基因选择性表达的机器。虽然典型的感觉功能是由蛋白质完成的，但最近发现的调节电路涉及被称为核糖开关的mRNA区域，能够直接和特异性地结合细胞代谢物。核糖开关存在于生命的所有王国中，在细菌中含量极高，包括病原菌，它们直接表达许多重要基因，对各种代谢物做出反应，包括辅酶、氨基酸、糖和核苷酸。每个核糖开关被折叠成一个进化保守的三维结构，通过与同源代谢物的相互作用稳定下来。由于核糖开关通过其结构中的构象重排来调节基因的表达，我们的研究重点放在确定核糖开关配体复合体的三维结构上。这些结构将揭示核糖开关控制的基因表达的分子原理，并可能有助于合理设计新型代谢物类抗生素。