Abstract

BACKGROUND: 2'-5' Oligoadenylate synthetases are interferon-induced enzymes important for antiviral cell defense. Tetramer formation of human OAS1 is essential for the catalytic activity of the enzyme. However, no structure of any oligomeric OAS1 protein has yet been solved and the structural organization of the catalytically active tetramers is not known. MATERIAL/METHODS: Using a novel conjunction of comparative modeling, molecular surface analysis, and sequence analysis, high-resolution models of the known isoforms of human OAS1 were prepared. RESULTS: The resulting models suggest different oligomeric states for the p40, p46, and p48 isoforms as well as a significant difference in enzymatic activity between the p46 and p40/p48 isoforms. CONCLUSIONS: The differences in enzymatic activity could result in different susceptibility to viral infection in cells expressing individual isoforms. The models are consistent with the published biochemical data on human OAS1. The results also suggest that the structure of the active OAS2 dimers would be equivalent to that of p40 OAS1 tetramers.

Keywords: 2',5'-Oligoadenylate Synthetase - chemistry, 2',5'-Oligoadenylate Synthetase - chemistry, Computational Biology, Dimerization, Isoenzymes - chemistry, Models, Molecular, Protein Conformation