A homology model of human interferon alpha-2.
An atomic coordinate five alpha-helix three-dimensional model is presented for human interferon alpha-2 (HuIFN alpha 2). The HuIFN alpha 2 structure was constructed from murine interferon beta (MuIFN beta) by homology modeling using the STEREO and IMPACT programs. The HuIFN alpha 2 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 HuIFN alpha 2 with endoproteinase Lys-C demonstrated rapid cleavage at K31, which is consistent with the presence of this residue in a loop in the proposed HuIFN alpha 2 model. Based on this model structure potential receptor binding sites are identified.
Murgolo
N J
NJ
Schering-Plough Research Institute, Kenilworth, New Jersey 07033.
Windsor
W T
WT
Hruza
A
A
Reichert
P
P
Tsarbopoulos
A
A
Baldwin
S
S
Huang
E
E
Pramanik
B
B
Ealick
S
S
Trotta
P P
PP
D000595:Amino Acid Sequence; D006801:Humans; D016898:Interferon-alpha / Q000737:chemistry / Q000648:ultrastructure*; D016899:Interferon-beta / Q000648:ultrastructure; D008239:Lysine / Q000737:chemistry; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D017386:Sequence Homology, Amino Acid; D014357:Trypsin / Q000494:pharmacology
D016898:Interferon-alpha; D016899:Interferon-beta; D014357:Trypsin; D008239:Lysine