The radical-SAM enzyme Viperin catalyzes reductive addition of a 5′-deoxyadenosyl radical to UDP-glucose in vitro

Kourosh Honarmand Ebrahimi, Stephen B. Carr, James McCullagh, James Wickens, Nicholas H. Rees, James Cantley, Fraser A. Armstrong

Research output: Contribution to journalLetter

13 Citations (Scopus)

Abstract

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 languageEnglish
Pages (from-to)2394-2405
Number of pages12
JournalFEBS Letters
Volume591
Issue number16
Early online date28 Jul 2017
DOIs
Publication statusPublished - Aug 2017

Keywords

  • immune system
  • radical-SAM
  • Viperin

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    Honarmand Ebrahimi, K., Carr, S. B., McCullagh, J., Wickens, J., Rees, N. H., Cantley, J., & Armstrong, F. A. (2017). The radical-SAM enzyme Viperin catalyzes reductive addition of a 5′-deoxyadenosyl radical to UDP-glucose in vitro. FEBS Letters, 591(16), 2394-2405. https://doi.org/10.1002/1873-3468.12769