6B4C
Structure of Viperin from Trichoderma virens
Summary for 6B4C
| Entry DOI | 10.2210/pdb6b4c/pdb |
| Descriptor | Viperin, SULFATE ION, CITRATE ANION, ... (4 entities in total) |
| Functional Keywords | enzyme, radical sam, antiviral, antiviral protein |
| Biological source | Hypocrea virens (strain Gv29-8 / FGSC 10586) (Gliocladium virens) |
| Total number of polymer chains | 12 |
| Total formula weight | 414154.49 |
| Authors | Huang, R.H.,Selvadurai, K. (deposition date: 2017-09-26, release date: 2018-07-25, Last modification date: 2024-03-13) |
| Primary citation | Chakravarti, A.,Selvadurai, K.,Shahoei, R.,Lee, H.,Fatma, S.,Tajkhorshid, E.,Huang, R.H. Reconstitution and substrate specificity for isopentenyl pyrophosphate of the antiviral radical SAM enzyme viperin. J.Biol.Chem., 293:14122-14133, 2018 Cited by PubMed Abstract: Viperin is a radical SAM enzyme that has been shown to possess antiviral activity against a broad spectrum of viruses; however, its molecular mechanism is unknown. We report here that recombinant fungal and archaeal viperin enzymes catalyze the addition of the 5'-deoxyadenosyl radical (5'-dA) to the double bond of isopentenyl pyrophosphate (IPP), producing a new compound we named adenylated isopentyl pyrophosphate (AIPP). The reaction is specific for IPP, as other pyrophosphate compounds involved in the mevalonate biosynthetic pathway did not react with 5'-dA Enzymatic reactions employing IPP derivatives as substrates revealed that any chemical change in IPP diminishes its ability to be an effective substrate of fungal viperin. Mutational studies disclosed that the hydroxyl group on the side chain of Tyr-245 in fungal viperin is the likely source of hydrogen in the last step of the radical addition, providing mechanistic insight into the radical reaction catalyzed by fungal viperin. Structure-based molecular dynamics (MD) simulations of viperin interacting with IPP revealed a good fit of the isopentenyl motif of IPP to the active site cavity of viperin, unraveling the molecular basis of substrate specificity of viperin for IPP. Collectively, our findings indicate that IPP is an effective substrate of fungal and archaeal viperin enzymes and provide critical insights into the reaction mechanism. PubMed: 30030381DOI: 10.1074/jbc.RA118.003998 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.795 Å) |
Structure validation
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