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Journal of Virology, August 2006, p. 7706-7713, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.00521-06

The Structure of G4, the Poxvirus Disulfide Oxidoreductase Essential for Virus Maturation and Infectivity

Hua-Poo Su, David Yin-wei Lin,{dagger} and David N. Garboczi*

Structural Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12441 Parklawn Drive, Rockville, Maryland 20852

Received 13 March 2006/ Accepted 10 May 2006

The possibility of the release of smallpox virus into a predominantly nonimmunized population highlights the importance of understanding poxvirus biology. Poxviruses encode a conserved pathway that is required to oxidize disulfide bonds in nascent viral proteins that fold in the reducing environment of the eukaryotic host cytoplasm. We present the structure of the last enzyme of the vaccinia virus pathway, G4, which is almost identical in smallpox virus. G4 catalyzes the formation of disulfide bonds in proteins that are critical for virus maturation and host cell infection. G4 contains a thioredoxin fold and a Cys-X-X-Cys active site. In solution, G4 monomers and dimers are observed. In the crystal, G4 is found as a dimer that buries 4,500 Å2 in the interface and occludes the active site, which could protect the reactive disulfide from reduction in the cytoplasm. The structure serves as a model for drug design targeting viral disulfide bond formation.

* Corresponding author. Mailing address: 12441 Parklawn Dr., Rockville, MD 20852. Phone: (301) 496-4773. Fax: (301) 402-0284. E-mail: dgarboczi{at}niaid.nih.gov.

{ddagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{dagger} Present address: Purdue University, 175 S. University Street, West Lafayette, IN 47907-2063.

Journal of Virology, August 2006, p. 7706-7713, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.00521-06




This article has been cited by other articles:

  • Van Vliet, K., Mohamed, M. R., Zhang, L., Villa, N. Y., Werden, S. J., Liu, J., McFadden, G. (2009). Poxvirus Proteomics and Virus-Host Protein Interactions. Microbiol. Mol. Biol. Rev. 73: 730-749 [Abstract] [Full Text]  


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