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Reversible oxidative modification as a mechanism for regulating retroviral protease dimerization and activation.

ABSTRACT: 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.

SUBMITTER: Davis DA

PROVIDER: S-EPMC149757 | biostudies-literature | 2003 Mar

REPOSITORIES: biostudies-literature

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Reversible oxidative modification as a mechanism for regulating retroviral protease dimerization and activation.

Davis David A DA Brown Cara A CA Newcomb Fonda M FM Boja Emily S ES Fales Henry M HM Kaufman Joshua J Stahl Stephen J SJ Wingfield Paul P Yarchoan Robert R

Journal of virology 20030301 5

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 s ...[more]

PMID: 12584357

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