Enzymes
| UniProtKB help_outline | 3 proteins |
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- Name help_outline AH2 Identifier CHEBI:17499 Charge 0 Formula RH2 SMILEShelp_outline *([H])[H] 2D coordinates Mol file for the small molecule Search links Involved in 2,713 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline CTP Identifier CHEBI:37563 (Beilstein: 4732530) help_outline Charge -4 Formula C9H12N3O14P3 InChIKeyhelp_outline PCDQPRRSZKQHHS-XVFCMESISA-J SMILEShelp_outline Nc1ccn([C@@H]2O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]2O)c(=O)n1 2D coordinates Mol file for the small molecule Search links Involved in 78 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline S-adenosyl-L-methionine Identifier CHEBI:59789 Charge 1 Formula C15H23N6O5S InChIKeyhelp_outline MEFKEPWMEQBLKI-AIRLBKTGSA-O SMILEShelp_outline C[S+](CC[C@H]([NH3+])C([O-])=O)C[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1cnc2c(N)ncnc12 2D coordinates Mol file for the small molecule Search links Involved in 842 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 3'-deoxy-3',4'-didehydro-CTP Identifier CHEBI:166821 Charge -4 Formula C9H10N3O13P3 InChIKeyhelp_outline DGUQXKKDZHTKIE-HTRCEHHLSA-J SMILEShelp_outline NC1=NC(=O)N(C=C1)[C@@H]1OC(COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)=C[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 5'-deoxyadenosine Identifier CHEBI:17319 (CAS: 4754-39-6) help_outline Charge 0 Formula C10H13N5O3 InChIKeyhelp_outline XGYIMTFOTBMPFP-KQYNXXCUSA-N SMILEShelp_outline C[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1cnc2c(N)ncnc12 2D coordinates Mol file for the small molecule Search links Involved in 66 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline A Identifier CHEBI:13193 Charge Formula R SMILEShelp_outline * 2D coordinates Mol file for the small molecule Search links Involved in 2,783 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,048 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline L-methionine Identifier CHEBI:57844 Charge 0 Formula C5H11NO2S InChIKeyhelp_outline FFEARJCKVFRZRR-BYPYZUCNSA-N SMILEShelp_outline CSCC[C@H]([NH3+])C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 118 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:65944 | RHEA:65945 | RHEA:65946 | RHEA:65947 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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A naturally occurring antiviral ribonucleotide encoded by the human genome.
Gizzi A.S., Grove T.L., Arnold J.J., Jose J., Jangra R.K., Garforth S.J., Du Q., Cahill S.M., Dulyaninova N.G., Love J.D., Chandran K., Bresnick A.R., Cameron C.E., Almo S.C.
Viral infections continue to represent major challenges to public health, and an enhanced mechanistic understanding of the processes that contribute to viral life cycles is necessary for the development of new therapeutic strategies <sup>1</sup> . Viperin, a member of the radical S-adenosyl-L-meth ... >> More
Viral infections continue to represent major challenges to public health, and an enhanced mechanistic understanding of the processes that contribute to viral life cycles is necessary for the development of new therapeutic strategies <sup>1</sup> . Viperin, a member of the radical S-adenosyl-L-methionine (SAM) superfamily of enzymes, is an interferon-inducible protein implicated in the inhibition of replication of a broad range of RNA and DNA viruses, including dengue virus, West Nile virus, hepatitis C virus, influenza A virus, rabies virus <sup>2</sup> and HIV<sup>3,4</sup>. Viperin has been suggested to elicit these broad antiviral activities through interactions with a large number of functionally unrelated host and viral proteins<sup>3,4</sup>. Here we demonstrate that viperin catalyses the conversion of cytidine triphosphate (CTP) to 3'-deoxy-3',4'-didehydro-CTP (ddhCTP), a previously undescribed biologically relevant molecule, via a SAM-dependent radical mechanism. We show that mammalian cells expressing viperin and macrophages stimulated with IFNα produce substantial quantities of ddhCTP. We also establish that ddhCTP acts as a chain terminator for the RNA-dependent RNA polymerases from multiple members of the Flavivirus genus, and show that ddhCTP directly inhibits replication of Zika virus in vivo. These findings suggest a partially unifying mechanism for the broad antiviral effects of viperin that is based on the intrinsic enzymatic properties of the protein and involves the generation of a naturally occurring replication-chain terminator encoded by mammalian genomes. << Less
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Prokaryotic viperins produce diverse antiviral molecules.
Bernheim A., Millman A., Ofir G., Meitav G., Avraham C., Shomar H., Rosenberg M.M., Tal N., Melamed S., Amitai G., Sorek R.
Viperin is an interferon-induced cellular protein that is conserved in animals<sup>1</sup>. It has previously been shown to inhibit the replication of multiple viruses by producing the ribonucleotide 3'-deoxy-3',4'-didehydro (ddh)-cytidine triphosphate (ddhCTP), which acts as a chain terminator fo ... >> More
Viperin is an interferon-induced cellular protein that is conserved in animals<sup>1</sup>. It has previously been shown to inhibit the replication of multiple viruses by producing the ribonucleotide 3'-deoxy-3',4'-didehydro (ddh)-cytidine triphosphate (ddhCTP), which acts as a chain terminator for viral RNA polymerase<sup>2</sup>. Here we show that eukaryotic viperin originated from a clade of bacterial and archaeal proteins that protect against phage infection. Prokaryotic viperins produce a set of modified ribonucleotides that include ddhCTP, ddh-guanosine triphosphate (ddhGTP) and ddh-uridine triphosphate (ddhUTP). We further show that prokaryotic viperins protect against T7 phage infection by inhibiting viral polymerase-dependent transcription, suggesting that it has an antiviral mechanism of action similar to that of animal viperin. Our results reveal a class of potential natural antiviral compounds produced by bacterial immune systems. << Less
Nature 589:120-124(2021) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.