Theoretical analysis of conformation and active sites of interferons.

Seven methods for prediction of protein secondary structures [1, 2, 14, 21, 22, 30, 31] were used for analysis of conformation of alpha- and beta-interferons (IFN-alpha and -beta). The results of the analysis indicate that the dominant secondary structure of IFNs-alpha and -beta is an alpha-helix. Five segments of the helix predicted by all the methods used have been identified. Using the method of Vonderviszt and Simon in IFNs-alpha and -beta two domains are predicted, the border between them lying at the region of amino acid (aa) residues 100-110. Comparison of primary structures of IFNs-alpha, -beta and -omega of different origin revealed two peculiar regions of conservative positions. In the first region, restricted to the N-terminal domain, 9 of 13 conservative positions are occupied by hydrophilic residues. In the second region, restricted to the C-terminal domain, all 8 conservative positions are occupied by hydrophobic residues. The C-terminal domain of the IFNs-alpha (aa residues 116-165) has been found to have a statistically valid homology (36%, probability of random coincidence is 5 x 10(-4) with prothymosin-alpha 1 (residues 1-47). The results of the theoretical analysis as compared to the experimental data available suggest the existence of at least two active sites in IFNs-alpha, beta and omega.(ABSTRACT TRUNCATED AT 250 WORDS)