Collaborative Research: Protein Arginine Methylation

合作研究：蛋白质精氨酸甲基化

• 批准号: 1626860
• 负责人: Orlando Acevedo
• 金额: $ 11.79万
• 依托单位: University of Miami
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2018-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1626860&HistoricalAwards=false
• 关键词: Collaborative; Research; Protein; Arginine; Methylation

The addition of one or more specific markers to proteins by enzymes known as protein arginine methyltransferases (PRMTs) allows cells to adapt to their ever-changing environments. Biological pathways responsible for development, the response to hormones and viruses, cancer and cardiovascular disease are all impacted by exactly how PRMTs carry out their additions to protein targets. The studies will characterize how the individual members of the PRMT family dictate very specific product formation, for example, one versus two additions, in order to direct the result that is required in the cell. The proposed strategy will integrate both computational modeling and ?at-the-bench? biochemical experiments to reveal just how product formation takes place for two members of the PRMT family. The results of these studies will provide foundational information that is required for novel inhibitor development, as well as allow for an understanding of the sophisticated role PRMTs play in cellular signaling. The studies will provide cross training for students in both computational and wet biochemistry experimental strategies, as well as provide the opportunity for undergraduates to receive on-the-job training in the lab, preparing them for the STEM workforce. With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Joan Hevel and Dr. Orlando Acevedo to characterize the mechanism of protein arginine monomethylation versus dimethylation using advanced computational and biophysical techniques. The role of sterics, dynamics, and mode of substrate binding in determining which of two different methylation products the protein arginine methyltransferases form will be determined. Information from this study will provide new insight into the sophisticated control of product formation that is required to maintain appropriate patterns of signaling in cells.

通过蛋白质精氨酸甲基转移酶（PRMT）将一种或多种特异性标记物添加到蛋白质中，使细胞能够适应不断变化的环境。 负责发育的生物途径，对激素和病毒的反应，癌症和心血管疾病都受到PRMT如何添加蛋白质靶点的影响。 这些研究将表征PRMT家族的各个成员如何决定非常特定的产物形成，例如，一次添加与两次添加，以指导细胞中所需的结果。 所提出的战略将结合计算建模和？坐在法官席上生物化学实验揭示了PRMT家族的两个成员如何形成产物。 这些研究的结果将提供新的抑制剂开发所需的基础信息，并允许了解PRMT在细胞信号传导中发挥的复杂作用。 这些研究将为学生提供计算和湿生物化学实验策略的交叉培训，并为本科生提供在实验室接受在职培训的机会，为STEM劳动力做好准备。有了这个奖项，化学部的生命过程计划的化学资助博士琼Hevel和博士奥兰多阿切韦多，以表征蛋白质精氨酸单甲基化与二甲基化的机制，使用先进的计算和生物物理技术。 空间，动力学，和模式的底物结合在确定这两个不同的甲基化产物的蛋白质精氨酸甲基转移酶的形式的作用将被确定。 这项研究的信息将提供新的见解，复杂的控制产品的形成，需要保持适当的模式，在细胞中的信号。