NMR STUDIES OF ISOTOPICALLY ENRICHED HUMAN INTERLEUKIN 5

我们已经启动了一项旨在获得解决方案的研究 人白介素5的结构。白介素5是一种同源二聚体 分子量为25kDalton的蛋白质。它是独一无二的 参与造血的细胞因子，因为它在 嗜酸性粒细胞分化。它是在提交以下文件时诱导的 异物或寄生虫。因此，它已成为 药物设计在缓解哮喘方面的努力，这是一种 通常与嗜酸性粒细胞增多症和炎症反应有关。 虽然晶体结构是已知的，但我们认为确定一个 一整套作业和解决方案结构将有助于 区域内小分子与蛋白质相互作用的研究 定点突变实验表明，这种突变在 受体相互作用。我们最初的努力集中在获得一个 利用合成基因实现蛋白质的高效表达 利用优化密码子使用和高产量表达的方法 向量。使用这个系统，我们已经获得了足够数量的 双标记白介素5开始三重共振分配和 结构说明。

We have initiated a study directed at obtaining the solution structure of human interleukin-5. Interleukin-5 is a homodimeric protein with a molecular weight of 25 kDaltons. It is unique among the cytokines involved in hematopoesis in that it is essential in eosinsophil differentiation. It is induced upon presentation of foreign bodies or parasites. As such it has become a key target for drug design efforts in the alleviation of asthma, a condition which is often associated with eosinophilia and the inflammatory response. Although a crystal structure is known, we believe determining a complete set of assignments and a solution structure will facilitate the study of small molecule interactions with the protein in regions that site-directed mutagenesis experiments indicate are essential in receptor interaction. Our efforts initially focused on obtaining a high yield expression system for the protein using a synthetic gene approach utilizing optimized codon usage and a high yield expression vector. Using this system we have obtained sufficient quantities of doubly labeled interleukin-5 to begin triple resonance assignment and structure elucidation.