Viperin is an interferon-inducible radical S-adenosylmethionine (SAM) enzyme that inhibits viral replication. The Mordis group from the University Department of Medicine in collaboration with other colleagues, have recently determined crystal structures of an anaerobically prepared fragment of mouse viperin bound to a SAM analog, and to SAM cleavage products. Viperin has an alpha/beta-barrel fold with at its centre a [4Fe-4S] iron-suflur cluster. The active site architecture of viperin is consistent with the canonical mechanism of radical generation by radical SAM enzymes. Structure-based sequence alignments suggest that viperinsare highly conserved in vertebrates, and that fungi and many bacteria and archaebacteria express viperin orthologues with conserved active site residues. Viperin has structural similarity to several other radical SAM enzymes, including the molybdenum cofactor biosynthetic enzyme MoaA, which metabolizes GTP, and the RNA methyltransferase RlmN, which methylates specific nucleotides in rRNA and tRNA. Based on our structural analysis, we conclude that the substrate of viperin is a nucleoside triphosphate. We speculate that viperin may restrict viral infection either by degrading viral RNA, or by depleting nucleosides, which are required for viral genomic RNA replication and as a source of energy, in infected cells. The work has recently been published in the Proceedings of the National Academy of Sciences READ MORE
The crystal structure of viperin, an interferon-induced antiviral radical SAM enzyme. The structure suggests that viperin chemically modifies nuceloside triphosphates in the cytosol upon induction by type I interferons. Viperin substrates may also include cellular or microbial RNAs.