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Viperin, a radical-S-adenosylmethionine (SAM) enzyme conserved from fungi to humans, can restrict replication of many viruses. Neither the molecular mechanism underlying the antiviral activity of Viperin, nor its exact physiological function, is understood: most importantly, no radical-SAM activity has been discovered for Viperin. Here, using electron paramagnetic resonance (EPR) spectroscopy, mass spectrometry, and NMR spectroscopy, we show that uridine diphosphate glucose (UDP-glucose) is a substrate of a fungal Viperin (58% pairwise identity with human Viperin at the amino acid level) in vitro. Structural homology modeling and docking experiments reveal a highly conserved binding pocket in which the position of UDP-glucose is consistent with our experimental data regarding catalytic addition of a 5'-deoxyadenosyl radical and a hydrogen atom to UDP-glucose.

Original publication

DOI

10.1002/1873-3468.12769

Type

Journal article

Journal

FEBS Lett

Publication Date

08/2017

Volume

591

Pages

2394 - 2405

Keywords

Viperin, immune system, radical-SAM, Amino Acid Sequence, Biocatalysis, Conserved Sequence, Deoxyadenosines, Free Radicals, Fungal Proteins, Hydrogen, Molecular Docking Simulation, Oxidation-Reduction, Protein Conformation, S-Adenosylmethionine, Sordariales, Uridine Diphosphate Glucose