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

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.