PDBsum entry 6b4c

Antiviral protein

PDB id: 6b4c

Contents

Protein chains

(+ 6 more) 259 a.a.

Ligands

SO4 ×24

FLC ×12

Waters ×561

PDB id:

6b4c

Name:

Antiviral protein

Title:

Structure of viperin from trichoderma virens

Structure:

Viperin. Chain: a, b, c, d, e, f, g, h, i, j, k, l. Engineered: yes

Source:

Hypocrea virens (strain gv29-8 / fgsc 10586). Gliocladium virens. Organism_taxid: 413071. Strain: gv29-8 / fgsc 10586. Gene: trividraft_58105. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.80Å R-factor: 0.190 R-free: 0.211

Authors:

R.H.Huang,K.Selvadurai

Key ref:

A.Chakravarti et al. (2018). Reconstitution and substrate specificity for isopentenyl pyrophosphate of the antiviral radical SAM enzyme viperin. J Biol Chem, 293, 14122-14133. PubMed id: 30030381 DOI: 10.1074/jbc.RA118.003998

Date:

26-Sep-17 Release date: 25-Jul-18

Protein chains

G9MQB8  (G9MQB8_HYPVG) -  Radical SAM core domain-containing protein from Hypocrea virens (strain Gv29-8 / FGSC 10586)

Seq: 308 a.a.

Struc: 259 a.a.

DOI no: 10.1074/jbc.RA118.003998

J Biol Chem 293:14122-14133 (2018)

PubMed id: 30030381

Reconstitution and substrate specificity for isopentenyl pyrophosphate of the antiviral radical SAM enzyme viperin.

A.Chakravarti, K.Selvadurai, R.Shahoei, H.Lee, S.Fatma, E.Tajkhorshid, R.H.Huang.

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.