title: 2'-5' oligoadenylate synthetase shares active site architecture with the archaeal CCA-adding enzyme.
abstract: The 2'-5' oligoadenylate synthetases (OAS) are interferon-induced antiviral enzymes that recognise virally produced dsRNA and initiate an RNA destabilisation within the infected cell. We compared the structure of OAS to that of poly adenosine polymerase (PAP) and the class I CCA-adding enzyme from Archeoglobus fulgidus (AfCCA). This comparison revealed a strong structural homology between the three enzyme families. In particular, the active sites of OAS and CCA class I enzymes are highly conserved. We conducted an extensive mutagenesis of amino acid residues within the putative active site in OAS, thereby identifying enzymatically important residues and confirming the common active site architecture for OAS and the AfCCA. Our findings also have profound implications for our understanding of the evolutionary origin of the OAS enzymes and suggest that the OAS proteins diverged from a common 3'-specific ancestor at the beginning of metazoan evolution.
authors.affiliation: Centre for Structural Biology, Department of Molecular Biology, University of Aarhus, Gustav Wieds vej 10C, 8000 Aarhus, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Torralba
authors.forename: J
authors.initials: J
authors.lastname: Sojat
authors.forename: R
authors.initials: R
authors.lastname: Hartmann
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000737:chemistry* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000596:Amino Acids; D000818:Animals; D019611:Archaeoglobus fulgidus / Q000201:enzymology*; D001665:Binding Sites; D019143:Evolution, Molecular; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry; D009154:Mutation / Q000235:genetics; D012316:RNA Nucleotidyltransferases / Q000737:chemistry*; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D013552:Swine; D013698:Templates, Genetic
chemical_list: D000596:Amino Acids; D050505:Mutant Proteins; D000255:Adenosine Triphosphate; D012316:RNA Nucleotidyltransferases; C023198:tRNA nucleotidyltransferase; D015088:2',5'-Oligoadenylate Synthetase