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Journal of Virology, March 2003, p. 3319-3325, Vol. 77, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.5.3319-3325.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Reversible Oxidative Modification as a Mechanism for Regulating Retroviral Protease Dimerization and Activation

David A. Davis,1* Cara A. Brown,1 Fonda M. Newcomb,1,{dagger} Emily S. Boja,2 Henry M. Fales,2 Joshua Kaufman,3 Stephen J. Stahl,3 Paul Wingfield,3 and Robert Yarchoan1

HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute,1 Laboratory of Biophysical Chemistry, National Heart, Lung, and Blood Institute,2 Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 208923

Received 30 August 2002/ Accepted 20 November 2002

Human immunodeficiency virus protease activity can be regulated by reversible oxidation of a sulfur-containing amino acid at the dimer interface. We show here that oxidation of this amino acid in human immunodeficiency virus type 1 protease prevents dimer formation. Moreover, we show that human T-cell leukemia virus type 1 protease can be similarly regulated through reversible glutathionylation of its two conserved cysteine residues. Based on the known three-dimensional structures and multiple sequence alignments of retroviral proteases, it is predicted that the majority of retroviral proteases have sulfur-containing amino acids at the dimer interface. The regulation of protease activity by the modification of a sulfur-containing amino acid at the dimer interface may be a conserved mechanism among the majority of retroviruses.


* Corresponding author. Mailing address: NCI-CCR, 9000 Rockville Pike, Bldg. 10, Rm. 10S255, NIH, Bethesda, MD 20892-1868. Phone: (301) 402-3630. Fax: (301) 402-3645. E-mail: dadavis{at}helix.nih.gov.

{dagger} Present address: Perkin Elmer Life Sciences, Boston, MA 02118.


Journal of Virology, March 2003, p. 3319-3325, Vol. 77, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.5.3319-3325.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.