TY - JOUR
T1 - The radical-SAM enzyme Viperin catalyzes reductive addition of a 5′-deoxyadenosyl radical to UDP-glucose in vitro
AU - Honarmand Ebrahimi, Kourosh
AU - Carr, Stephen B.
AU - McCullagh, James
AU - Wickens, James
AU - Rees, Nicholas H.
AU - Cantley, James
AU - Armstrong, Fraser A.
PY - 2017/8
Y1 - 2017/8
N2 - 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.
AB - 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.
KW - immune system
KW - radical-SAM
KW - Viperin
UR - http://www.scopus.com/inward/record.url?scp=85028395690&partnerID=8YFLogxK
U2 - 10.1002/1873-3468.12769
DO - 10.1002/1873-3468.12769
M3 - Letter
C2 - 28752893
AN - SCOPUS:85028395690
VL - 591
SP - 2394
EP - 2405
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 16
ER -