A HOMOLOGY MODEL OF HUMAN INTERFERON-ALPHA-2

An atomic coordinate five alpha-helix three-dimensional model is presented for human interferon alpha-2 (HuIFNalpha2). The HuIFNalpha2 structure was constructed from murine interferon beta (MuIFNbeta) by homology modeling using the STEREO and IMPACT programs. The HuIFNalpha2 model is consistent with its known biochemical and biophysical properties including epitope mapping. Lysine residues predicted to be buried in the model were primarily unreactive with succinimidyl-7-amino-4-methylcoumarin-3-acetic acid (AMCA-NHS), a lysine modification agent, as shown by mass spectrometric analysis of tryptic digests. N-terminal sequence analysis of polypeptides generated by limited digestion of HuIFNalpha2 with endoproteinase Lys-C demonstrated rapid cleavage at K31, which is consistent with the presence of this residue in a loop in the proposed HuIFNalpha2 model. Based on this model structure potential receptor binding sites are identified. (C) 1993 Wiley-Liss, Inc.