NOVEL NMR STUDIES OF HEME PROTEINS INVOLVED IN ANEMIA

细胞色素b5是负责 维持血红蛋白处于降低的功能状态。最近，我们 已经发现证据表明脊椎的变化 细胞色素b5的动态变化可能有助于这一生理作用。我们 测量了还原电势与温度的关系 使用范特霍夫式的数据分析方法，我们发现 与氧化相关的熵变是正的。我们还有 根据氢交换动力学的测量，发现 氢键强度发生了大范围的变化 在整个分子中被氧化。初步测量 在还原和氧化状态下的主干动力学的差异 蛋白质也符合这一假说。通过更多 我们希望得到的与场相关的15N驰豫数据的详细分析 能够定量地将主干动态对 使用关系式计算与氧化相关的熵变 由Akke等人开发。(1993年)。

Cytochrome b5 is the terminal electron donor responsible for maintaining hemoglobin in its reduced functional state. Recently, we have found evidence that suggests that changes in the backbone dynamics of cytochrome b5 may facilitate this physiological role. We have measured the temperature dependence of the reduction potential and using a van't Hoff like analysis of the data, we find that the entropy change associated with oxidation is positive. We have also found, based on measurements of deuterium exchange kinetics, that large scale changes in the strengths of hydrogen bonds occur throughout the molecule upon oxidation. Preliminary measurements of differences in backbone dynamics in reduced and oxidized states of the protein are also consistent with this hypothesis. Through more detailed analyses of field dependent 15N relaxation data we hope to be able to quantitatively relate the contribution of backbone dynamics to the entropy change associated with oxidation using relationships developed by Akke, et al. (1993).