5VSM

Crystal structure of viperin with bound [4Fe-4S] cluster, 5'-deoxyadenosine, and L-methionine

Summary for 5VSM

• Entry DOI: 10.2210/pdb5vsm/pdb
• Related: 5VSL
• Descriptor: Radical S-adenosyl methionine domain-containing protein 2, IRON/SULFUR CLUSTER, 5'-DEOXYADENOSINE, ... (5 entities in total)
• Functional Keywords: radical, s-adenosylmethionine, iron-sulfur cluster, antiviral response, antiviral protein
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 75125.72

Authors

Fenwick, M.K.,Li, Y.,Cresswell, P.,Modis, Y.,Ealick, S.E. (deposition date: 2017-05-11, release date: 2017-06-14, Last modification date: 2024-04-03)

Primary citation

Fenwick, M.K.,Li, Y.,Cresswell, P.,Modis, Y.,Ealick, S.E.
Structural studies of viperin, an antiviral radical SAM enzyme.
Proc. Natl. Acad. Sci. U.S.A., 114:6806-6811, 2017

PubMed Abstract: Viperin is an IFN-inducible radical -adenosylmethionine (SAM) enzyme that inhibits viral replication. We determined crystal structures of an anaerobically prepared fragment of mouse viperin (residues 45-362) complexed with -adenosylhomocysteine (SAH) or 5'-deoxyadenosine (5'-dAdo) and l-methionine (l-Met). Viperin contains a partial (βα)-barrel fold with a disordered N-terminal extension (residues 45-74) and a partially ordered C-terminal extension (residues 285-362) that bridges the partial barrel to form an overall closed barrel structure. Cys84, Cys88, and Cys91 located after the first β-strand bind a [4Fe-4S] cluster. The active site architecture of viperin with bound SAH (a SAM analog) or 5'-dAdo and l-Met (SAM cleavage products) is consistent with the canonical mechanism of 5'-deoxyadenosyl radical generation. The viperin structure, together with sequence alignments, suggests that vertebrate viperins are highly conserved and that fungi contain a viperin-like ortholog. Many bacteria and archaebacteria also express viperin-like enzymes with conserved active site residues. Structural alignments show that viperin is similar to several other radical SAM enzymes, including the molybdenum cofactor biosynthetic enzyme MoaA and the RNA methyltransferase RlmN, which methylates specific nucleotides in rRNA and tRNA. The viperin putative active site contains several conserved positively charged residues, and a portion of the active site shows structural similarity to the GTP-binding site of MoaA, suggesting that the viperin substrate may be a nucleoside triphosphate of some type.

PubMed: 28607080
DOI: 10.1073/pnas.1705402114

Experimental method

X-RAY DIFFRACTION (1.7 Å)