NMR STUDIES OF ISOTOPICALLY ENRICHED HUMAN INTERLEUKIN 5

我们已经开始了一项旨在获得解决方案的研究 人白细胞介素-5结构。 白细胞介素-5是一种同型二聚体， 分子量为25千道尔顿的蛋白质。 它是独一无二的， 细胞因子参与造血，因为它是必不可少的， 嗜酸性粒细胞分化 它是在呈现 异物或寄生虫。 因此，它已成为一个关键目标， 药物设计在缓解哮喘方面的努力， 通常与嗜酸性粒细胞增多和炎症反应有关。 虽然晶体结构是已知的，但我们相信确定一个 一套完整的作业和解决方案结构将有助于 小分子与蛋白质相互作用的研究 定点诱变实验表明， 受体相互作用 我们的努力最初集中在获得一个 使用合成基因的蛋白质的高产表达系统 利用优化的密码子使用和高产量表达的方法 vector. 使用这个系统，我们已经获得了足够数量的 双标记的白细胞介素-5开始三重共振分配， 结构解析

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.