PROBING THE INFLUENCE OF ARGININE METHYLATION ON THE MODULATION OF BIOMOLECULAR

探讨精氨酸甲基化对生物分子调节的影响

• 批准号: 7959721
• 负责人: Jason M Shearer
• 金额: $ 12.88万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959721
• 关键词: Affinity; Arginine; Autistic Disorder; Binding; Biological; Biological Process; Biomedical Research; Cells; Computer Retrieval of Information on Scientific Projects Database; Computing Methodologies; DNA; DNA Binding; DNA Structure; Disease; Failure; Funding; Gene Expression; Grant; Health; Human; Institution; Lead; Malignant Neoplasms; Methylation; Modeling; Nuclear; Nucleic Acid Binding; Nucleic Acids; Peptides; Post-Translational Protein Processing; Preparation; Prion Diseases; Property; Proteins; Research; Research Personnel; Resources; Source; United States National Institutes of Health; base; cofactor; electronic structure; functional group; guanidinium; protein complex; protein protein interaction; small molecule

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. Cells utilize weak biological interactions to control a multitude of biological processes. From a human health standpoint a failure in the precise control of these interactions can lead to a number of diseases ranging from cancer to prion diseases to autism. It has been shown that many proteins found in the nuclear region of cells, especially those that bind nucleic acids, undergo a post translational modification called arginine methylation. This indicates that arginine methylation is utilized to modulate gene expression, possibly by changing the binding affinity of the modified protein towards nucleic acids and other gene-expression proteins/cofactors. The magnitude of the change in the energetics and geometries of nucleic acid binding effected by arginine methylated proteins is poorly understood. The research proposed in this subproject is aimed at understanding the influence that arginine methylation has on controlling protein DNA and protein protein interactions. To these ends a number of small molecule, peptide, and protein based models that can bind 1) nucleic acids and 2) contain guanidinium-groups (the functional group of an arginine residue) will be prepared. The guanidinium group will be sequentially methylated, and the influence this has on the DNA binding properties of these model compounds, the subsequent structure of the DNA protein complex, and the strength of the DNA protein bonding interaction will be determined. In addition, high-level electronic structure computational methods will be utilized to both rationalize the results obtained from these studies and guide the preparation of the DNA-binding model compounds.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 细胞利用弱生物学相互作用来控制多种生物学过程。 从人类健康的角度来看，这些相互作用的精确控制失败会导致多种疾病，从癌症到病毒疾病再到自闭症。 已经表明，在细胞的核区域，尤其是结合核酸的核区域中发现了许多蛋白质，经历了一种称为精氨酸甲基化的翻译后修饰。 这表明精氨酸甲基化被用来调节基因表达，可能是通过改变改性蛋白对核酸和其他基因表达蛋白/辅助因子的结合亲和力。 鲜为人知地了解了精氨酸甲基化蛋白的核酸结合的能量和几何形状变化的大小。该次次运动中提出的研究旨在了解精氨酸甲基化对控制蛋白DNA和蛋白质蛋白质相互作用的影响。 在这些末端，可以制备许多可以结合的小分子，肽和基于蛋白质的模型1）核酸和2）含有鸟苷基团（精氨酸残基的官能团）。 鸟嘌呤组将被依次甲基化，并且将对这些模型化合物的DNA结合特性，DNA蛋白复合物的后续结构以及DNA蛋白键合的强度确定。 此外，将利用高级电子结构计算方法来合理化从这些研究获得的结果，并指导DNA结合模型化合物的制备。