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

被引：27

作者：

Ebrahimi, Kourosh Honarmand ^{[1
]}

Carr, Stephen B. ^{[2
,3
]}

McCullagh, James ^{[1
]}

Wickens, James ^{[1
]}

Rees, Nicholas H. ^{[1
]}

Cantley, James ^{[4
]}

Armstrong, Fraser A. ^{[1
]}

机构：

[1] Univ Oxford, Dept Chem, Oxford, England

[2] Rutherford Appleton Lab, Res Complex Harwell, Didcot, Oxon, England

[3] Univ Oxford, Dept Biochem, Oxford, England

[4] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England

来源：

FEBS LETTERS | 2017年 / 591卷 / 16期

基金：

英国工程与自然科学研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

immune system; radical-SAM; Viperin; S-ADENOSYLMETHIONINE ENZYMES; INTERFERON-INDUCIBLE PROTEIN; ANTIVIRAL PROTEIN; VIRUS-REPLICATION; BIOTIN SYNTHASE; PATHWAY; BIOSYNTHESIS; SUPERFAMILY; EXPRESSION; RESIDUES;

D O I：

10.1002/1873-3468.12769

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：2394 / 2405

页数：12

共 48 条

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Radical-mediated ring contraction in the biosynthesis of 7-deazapurines [J].