ANION DEPENDENT PROPERTIES OF TRANSFERRIN

转铁蛋白是一类重要的代谢转运蛋白 铁. 这些蛋白质可逆地结合两摩尔的铁，但为了做到这一点， 合适的阴离子也必须与蛋白质结合。 很少有人知道的 金属和阴离子结合位点的结构或释放机制， 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。 金属和阴离子结合位点将通过使用EPR和NMR来表征 各种阴离子和金属，例如，Cu（II）和VO（II）和Fe（III）， 蛋白质的衍生物。 这些信息将用于构建模型 对于金属的配位。 将确定哪些配体是 不稳定，因此对于金属离子释放是重要的。 特别是， 配位水的作用将通过NMR光谱和动力学研究 问题研究 各种药物如ATP或柠檬酸盐的作用机制， 促进铁释放的人血清转铁蛋白，将进行动力学研究 和光谱。 将采用NMR来绘制各种之间的距离 相对于金属中心的结合位点。 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 详细研究 次级阴离子结合位点的可能意义 将确定转铁蛋白的作用。 的催化作用 其它金属离子对铁从人血清转铁蛋白中释放的影响将被 评价为铁释放的可能机制。 这项全面的研究应有助于更好地了解这一机制 人血清转铁蛋白对代谢铁的摄取、运输和释放， 以及金属位点结构、阴离子、ATP和其他因素在 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.