Structure and dynamics of a predicted ferredoxin-like selenoprotein in Japanese encephalitis virus

Haizhen Andrew Zhong, Ethan Will Taylor

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Homologues of the selenoprotein glutathione peroxidase (GPx) have been previously identified in poxviruses and in RNA viruses including HIV-1 and hepatitis C virus (HCV). Sequence analysis of the NS4 region of Japanese encephalitis virus (JEV) suggests it may encode a structurally related but functionally distinct selenoprotein gene, more closely related to the iron-binding protein ferredoxin than to GPx, with three highly conserved UGA codons that align with essential Cys residues of ferredoxin. Comparison of the probe JEV sequence to an aligned family of ferredoxin sequences gave an overall 30.3% identity and 45.8% similarity, and was statistically significant at 4.9 S.D. (P < 10 -6) above the average score computed for randomly shuffled sequences. A 3-dimensional model of the hypothetical JEV protein (JEV model) was constructed by homology modeling using SYBYL, based upon a high resolution X-ray structure of ferredoxin (PDB code: 1awd). The JEV model and the model from 1awd were subsequently subjected to molecular dynamics simulations in aqueous medium using AMBER 6. The solution structure of the JEV model indicates that it could fold into a tertiary structure globally similar to ferredoxin 1awd, with RMSD between the averaged structures of 1.8 Å for the aligned regions. The modeling and MD simulations data also indicate that this structure for the JEV protein is energetically favorable, and that it could be quite stable at room temperature. This protein might play a role in JEV infection and replication via TNF and other cellular stimuli mediated via redox mechanisms.

Original languageEnglish (US)
Pages (from-to)223-231
Number of pages9
JournalJournal of Molecular Graphics and Modelling
Volume23
Issue number3
DOIs
StatePublished - Dec 1 2004
Externally publishedYes

Fingerprint

encephalitis
Selenoproteins
Ferredoxins
viruses
Viruses
proteins
glutathione
Glutathione Peroxidase
Proteins
hepatitis
Iron-Binding Proteins
human immunodeficiency virus
homology
data simulation
infectious diseases
genes
stimuli
RNA
Molecular dynamics

Keywords

  • Ferredoxin
  • Homology modeling
  • Japanese encephalitis virus
  • Molecular dynamics
  • Sequence analysis

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Spectroscopy
  • Atomic and Molecular Physics, and Optics

Cite this

Structure and dynamics of a predicted ferredoxin-like selenoprotein in Japanese encephalitis virus. / Zhong, Haizhen Andrew; Taylor, Ethan Will.

In: Journal of Molecular Graphics and Modelling, Vol. 23, No. 3, 01.12.2004, p. 223-231.

Research output: Contribution to journalArticle

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