NMR STUDIES OF RESPIRATORY PROTEINS AND MODEL SYSTEMS

这项研究的目的是为了更好地了解 结构，以及结构-功能关系，各种 肺组织中重要的氧转运和储氧蛋白 功能和疾病。最初的重点将放在分析 血红蛋白和肌红蛋白中铁-02键的性质。其他研究 将旨在解决无脊椎动物中Fe-0键的性质 氧气载体杂氰菊酯。我们将特别强调 铁-57和氧-17核磁的记录和分析 ~(57)Fe和~(170)C标记体系的核磁共振波谱 物种，如尖桩栅栏卟啉。通过这种方式，我们可以直接 从Fe-57化学位移的分析探讨Fe-0键的性质 (Sigma I)，化学屏蔽张量(Delta Sigma；Sigma 11，Sigma 22， Sigma 33)，桥(Fe-0-0；Fe-0-Fe)和 非桥联(Fe-0-0)氧及其核四极 耦合常数(e2qq/h)与电场梯度张量不对称性 参数(ETA)。E2qQ/h和ETA信息的分析将使用 Townes-Daily方法(最近应用于Si0-2)，以及对两者的分析 四极和化学位移数据还将使用经验和 非经验(INITO)方法。我们将首先确定57Fe化学成分 一系列模型化合物中的位移范围和松弛机制， 包括例如桩栅栏卟啉(E.F.(2-甲基咪唑)-Meso-四 (α，-邻联苯基苯基)卟啉合铁(II)02 采用高场傅里叶变换和连续波方法。这些 实验将为Hb和Mb系统的分析提供数据基础。 然后，它们将被扩展到顺磁和 杂氰菊酯的反铁磁耦合模型。解决方案 实验将辅以固态魔角旋转 实验中，得到了化学位移各向异性的值。类似 计划对170个有标签的系统进行模型系统研究，结果是 各向同性化学位移和电场梯度张量的情况 信息。利用双共振技术实现核四极共振 还将进行水平交叉实验。使用这个数据库， 然后我们将获得并解释铁-57和氧-17核磁共振(和NQR)。 MBO-2、HBO-2、HRO-2及相关体系的光谱。这样的结果应该 为检验各种理论提供有价值的数据(Weiss， Pauling，Case-Karplus，Olafson-Goddard)。

The objective of this research is to obtain a better understanding of the structure, and structure-function relations, of a variety of oxygen-transport and oxygen-storage proteins of importance in pulmonary function and disease. Initial emphasis will be placed on analysing the nature of Fe-02 bonding in hemoglobin and myoglobin. Additional studies will be aimed at solving the nature of Fe-0 bonding in the invertebrate oxygen carrier hemerythrin. Particular emphasis will be placed on recording and analyzing the iron-57 and oxygen-17 nuclear magnetic resonance (NMR) spectra of these systems using 57Fe and 170-labelled species, such as picket-fence porphyrins. In this way, we can directly probe the nature of Fe-0 bonding by analysis of iron-57 chemical shifts (sigma i), chemical shielding tensors (delta sigma; sigma 11, sigma 22, sigma 33), oxygen-17 chemical shifts of both bridging (Fe-0-0; Fe-0-Fe) and non-bridging (Fe-0-0) oxygens, together with their nuclear quadrupole coupling constants (e2qQ/h) and electric field gradient tensor asymmetry parameters (eta). Analysis of the e2qQ/h and eta information will use a Townes-Daily approach (recently applied to Si0-2), and analysis of both quadrupole and chemical shift data will also use empirical and non-empirical (initio) methods. We will first determine the 57Fe chemical shift ranges and relaxation mechanisms in a series of model compounds, including e.g. picket fence porphyrins (e.f. (2-methylimidazole)-meso-tetra (alpha,alpha,alpha,alpha,-0-pivalamidophenyl)porphyrinato iron(II) 02) using high-field Fourier transform and continuous-wave methods. These experiments will provide a data base for analysis of Hb and Mb systems. They will then be extended to investigation of paramagnetic and antiferromagnetically coupled models for hemerythrin. The solution experiments will be supplemented with solid-state magic-angle spinning experiments, to yield values of the chemical shift anisotropy. Similar model system studies are planned for 170-labelled systems, yielding in this case both isotropic chemical shift and electric field gradient tensor information. Nuclear quadrupole resonance using double-resonance level-crossing experiments will also be performed. Using this data base, we will then obtain and interpret the iron-57 and oxygen-17 NMR (and NQR) spectra of Mbo-2, Hbo-2, Hro-2, and related systems. Such results should provide valuable data with which to test the various theories (Weiss, Pauling, Case-Karplus, Olafson-Goddard) of Fe-0 bonding in hemme proteins.