EXAFS STUDIES OF MIXED METAL HYBRID HEMOGLOBINS

我们正在进行扩展X射线吸收精细结构 国家实验室的混合金属杂交血红蛋白的EXAFS研究 同步加速器光源 混合金属杂交血红蛋白是 血红蛋白四聚体，其中四个血红素离子中的一个或多个具有 被另一种金属取代，并作为中间体的模拟物， 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件， 每个氧中间体中的四个金属中心中的每一个 约束力 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 在阿尔伯特·爱因斯坦医学院进行。 ESEEM 研究检查了金属-双氧键的电子结构， 补充了EXAFS实现的键长测量 谱 UV RR研究检查色氨酸残基， 混合金属杂合血红蛋白的亚基界面作为 鉴定四聚体的四级状态的手段。 的EXAFS 因此，研究是详细调查的关键组成部分 霍夫血红蛋白四聚体的四级状态如何影响 四种金属的结构及其功能， 嗨，协同氧结合 增进对 人血红蛋白的结构-功能关系是研究人血红蛋白的结构和功能的基础。 血液替代品的设计，也可能提供一个模型， 生物大分子变构的结构基础 将军

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 Mixed metal hybrid hemoglobins are hemoglobin tetramers in which one or more of the four heme irons has been replaced by another metal and serve as mimics of intermediates of oxygen binding (see Section II).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.