EXAFS STUDIES OF MIXED METAL HYBRID HEMOGLOBINS

混合金属混合血红蛋白的 EXAFS 研究

• 批准号: 6120383
• 负责人: CAROLINE CAROLINE LEE
• 金额: --
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6120383
• 关键词: biological products; biomedical resource; cardiovascular system; proteins; spectrometry

We are carrying out extended X-ray absorption fine structure (EXAFS) studies of mixed metal hybrid hemoglobins at the National Synchrotron Light Source. Mixed metal hybrid hemoglobins are hemoglobin tetramers in which one or more of the four heme irons has been replaced by another metal and serve as mimics of intermediates of oxygen binding (see Section II). The proposed studies aim at obtaining a complete documentation of the metal-ligand bond lengths of each of the four metal centers in every intermediate of oxygen binding. Concurrent with the proposed EXAFS investigations, electron-spin echo envelope modulation (ESEEM) (an advanced EPR technique) and ultraviolet resonance Raman (UV RR) studies are being carried out at the Albert Einstein College of Medicine. The ESEEM studies examine the electronic structure of a metal-dioxygen bond and complement the bond length measurements achieved with EXAFS spectroscopy. The UV RR studies examine the tryptophan residues at the subunit interfaces of the mixed metal hybrid hemoglobins as a means of identifying the quaternary state of the tetramers. The EXAFS studies thus represent a crucial component of a detailed investigation Hof how the quaternary state of the hemoglobin tetramer affects the Hstructure of each of the four metals and consequently, its function, Hi.e., cooperative oxygen binding. Advancement in understanding the Hstructural-function relationship of human hemoglobin is essential for Hthe design of blood substitutes, and may also provide a model for the Hstructural basis of allostery in biological macromolecules in general.

我们正在进行扩展的X射线吸收精细结构 混合金属杂化血红蛋白的(EXAFS)研究 同步辐射光源。混合金属杂化血红蛋白 四个血红素铁中的一个或多个具有 已被另一种金属取代，并用作 氧结合(见第二节)。拟议的研究旨在 获得金属-配体键长的完整文档 氧的每一种中间体中的四个金属中心 有约束力的。在拟议的EXAFS调查的同时， 电子自旋回波包络调制(ESEEM)(一种先进的EPR 技术)和紫外共振拉曼(UV RR)研究正在进行中 是在阿尔伯特·爱因斯坦医学院进行的。ESEEM 研究检查了金属-二氧键的电子结构和 补充EXAFS获得的键长测量结果 光谱学。UV RR研究检查色氨酸残留量 混合金属杂化血红蛋白的亚基界面 识别四聚体的季态的方法。EXAFS 因此，研究是详细调查的重要组成部分。 Hof如何影响血红蛋白四聚体的四元状态 四种金属中每一种的结构，因此，它的功能， 例如，协同氧结合。在理解和理解 人血红蛋白的结构-功能关系是 为血液代用品的设计提供了一种模式，也可以为 生物大分子中变构的结构基础 将军。