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: 8360611
• 负责人: Jason M Shearer
• 金额: $ 7.67万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360611
• 关键词: Alzheimer' s Disease; Amyloid beta-Protein; Arginine; Biochemical; Biomedical Research; Copper; Funding; Goals; Grant; Investigation; Link; Literature; Metalloproteins; Metals; Methylation; Mutation; National Center for Research Resources; Principal Investigator; Prion Diseases; Prions; Production; Proteins; Reactive Oxygen Species; Research; Research Infrastructure; Resources; Source; United States National Institutes of Health; cost; neurotoxic

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Our original goals were to investigate the influence of arginine methylation on biomolecular interactions. This took a sideline as our investigations into Alzheimer's and prion disease were more fruitful. Therefore in our year three extension we altered our goals to probe the neurotoxic consequences of copper coordination to the prion protein and amyloid-beta peptides. Our goals are to: 1) determine the Cu(I) and Cu(II) coordination geometries within different isomorphs of the prion protein and amyloid-beta peptide as coordination geometry directly influence metal center reactivity, 2) probe how mutations to these proteins influence the coordination geometry of copper, 3) examine the ability of these copper-metalloproteins/metallopeptides to support catalytic reactive oxygen species production and 4) examine how the interaction between the copper, the prion-protein and amyloid-beta influence neurotxicity as such a link has been suggested in the biochemical literature.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 我们最初的目标是研究精氨酸甲基化对生物分子相互作用的影响。 当我们对阿尔茨海默氏症的调查和prion病更加富有成果时，这需要了一个边线。 因此，在我们的三年扩展中，我们改变了目标，以探测铜协调对prion蛋白和淀粉样蛋白β肽的神经毒性后果。 Our goals are to: 1) determine the Cu(I) and Cu(II) coordination geometries within different isomorphs of the prion protein and amyloid-beta peptide as coordination geometry directly influence metal center reactivity, 2) probe how mutations to these proteins influence the coordination geometry of copper, 3) examine the ability of these copper-metalloproteins/metallopeptides to support catalytic reactive氧生产和4）研究铜，蛋白蛋白和淀粉样蛋白β之间的相互作用如何影响神经毒性，因为在生化文献中已经提出了这种联系。