HOMOLOGY MODEL FOR ONCOSTATIN-M BASED ON NMR STRUCTURAL DATA

Oncostatin M (OM) is a member of the cytokine family which regulates t he proliferation and differentiation of a variety of cell types and in cludes interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and gra nulocyte-colony stimulating factor (G-CSF). This family of proteins ad opts a four-helix bundle fold with up-up-down-down topology and contai ns intramolecular disulfide bonds. Since an X-ray or NMR structure for OM is not currently available, a homology model for OM was determined from the X-ray structures of human growth hormone (hGH), LIF, and G-C SF where the alignment was based on secondary structure instead of seq uence. The OM secondary structure was determined from NMR structural d ata, and the secondary structures for hGH, LIF, and G-CSF were obtaine d from the reported X-ray structures. The resulting homology model was refined using sequential NOE distance C-13 restraints, chemical shift information, and a conformational database.