STRUCTURAL CHARACTERIZATION OF DE NOVO DESIGNED PEPTIDES

从头设计的肽的结构表征

• 批准号: 6658651
• 负责人: James E. Penner-Hahn
• 金额: $ 14.32万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6658651
• 关键词: biomaterials; biomedical resource; proteins; spectrometry; structural biology

Central to the understanding of metal protein interactions has been the question of whether metals enforce specific quarternary structure in proteins or whether proteins impart a specific coordination environment on the metal. Several amphiphilic, a-helical peptides have been designed de novo in order to permit a direct experimental determination of the factors which define metal protein interactions. By placing cysteine residues into the interior of the bundle to generate metal binding sites, we can test directly the stability of a particular bundle and the role of metal-ion coordination geometry in altering this stability. We have chosen a series of thiophilic metals that have coordination preferences including 2 coordinate (linear), 3 coordinate (trigonal) and 4 coordinate (tetrahedral) to deduce the thermodynamic stabilities associated with metal binding in these different environments. The metals to be studied are Zn(II), Hg(II), Cd(II), Cu(I), Ag(I) and Co(II). With the exception of the Co(II), which serves as a control, there is no technique other than EXAFS that can provide unambigous characterization of the local metal-site structure.

了解金属蛋白质相互作用的核心是 金属是否执行特定季度的问题 蛋白质的结构或蛋白质是否赋予特定的 金属上的配位环境。 几个两亲性、a-螺旋 肽是从头设计的，以便能够直接 金属蛋白定义因素的实验测定 互动。 通过将半胱氨酸残基放入 捆绑生成金属结合位点，我们可以直接测试 特定束的稳定性和金属离子的作用 协调几何形状改变了这种稳定性。 我们选择了一个 系列具有配位偏好的亲硫金属 包括2坐标（直线）、3坐标（三角）和4 坐标（四面体）来推导热力学稳定性 与这些不同环境中的金属结合有关。 这 要研究的金属有 Zn(II)、Hg(II)、Cd(II)、Cu(I)、Ag(I) 和 Co(II)。 除了作为对照的 Co(II) 外， 除了 EXAFS 之外，没有任何技术可以提供明确的 局部金属位点结构的表征。