ANION DEPENDENT PROPERTIES OF TRANSFERRIN

转铁蛋白是一类重要的运输代谢的蛋白质。 铁制的。这些蛋白质可逆地结合两个摩尔的铁，但为了做到这一点， 适当的阴离子也必须与蛋白质结合。人们对此知之甚少 金属和阴离子结合部位的结构或释放或 人血清转铁蛋白对铁的摄取。这里提出的研究解决了 这些重要的问题。 金属和阴离子结合部位将用EPR和核磁共振进行表征 各种阴离子和金属的光谱，例如，铜(II)、VO(II)和Fe(III)， 蛋白质的衍生品。这些信息将用于构建模型 关于金属的协调。将确定哪些配体是 不稳定，因此对金属离子释放很重要。特别是，可能的 配位水的作用将通过核磁共振光谱和动力学来检验 学习。如三磷酸腺苷或柠檬酸盐等各种药物的作用机制 人血清转铁蛋白促进铁释放的动力学研究 从光谱上看。核磁共振将被用来绘制不同物种之间的距离 相对于金属中心的结合部位。的结构要求 阴离子及其与蛋白质相互作用的基本性质将是 进行了详细的研究。次级阴离子结合位点的可能意义 转铁蛋白的作用将被确定。它的催化作用 其他金属离子对人血清转铁蛋白释放铁的影响 被评估为可能的铁释放机制。 这项全面的研究应该有助于更好地理解这种机制。 人血清转铁蛋白对代谢铁的摄取、运输和释放， 以及金属结构、阴离子、三磷酸腺苷等因素在其中所起的作用 这样的过程。

The transferrins are a class of important proteins which transport metabolic iron. These proteins reversibly bind two moles of iron but in order to do so a suitable anion must also bind to the protein. Little is known about the structure of the metal and anion binding sites or the mechanism of release or uptake of iron by human serotransferrin. The research proposed here addresses these important questions. The metal and anion binding sites will be characterized by using EPR and NMR spectroscopy of various anion and metal, e.g., Cu(II), and VO(II), and Fe(III), derivatives of the protein. This information will be used to construct a model for the coordination about the metal. It will be determined which ligands are labile and hence important for metal ion release. In particular, the possible role of coordinated water will be examined through NMR spectroscopy and kinetic studies. The mechanism of action of various agents such as ATP or citrate which facilitate iron release by human serotransferrin, will be studied kinetically and spectroscopically. NMR will be employed to map distances between various binding sites relative to the metal center. The structural requirement of the anion and the fundamental nature of its interaction with the protein will be studied in detail. The possible significance of secondary anion binding sites to the action of the transferrin will be determined. The catalytic effect of other metal ions on the release of iron from human serotransferrin will be evaluated as possible mechanism of iron release. This comprehensive study should lead to a better understanding of the mechanism of uptake, transport, and release of metabolic iron by human serotransferrin, and the role that metal site structure, anions, ATP, and other factors play in such processes.