title: 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.
authors.affiliation: HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. dadavis@helix.nih.gov
authors.forename: David A
authors.initials: DA
authors.lastname: Davis
authors.forename: Cara A
authors.initials: CA
authors.lastname: Brown
authors.forename: Fonda M
authors.initials: FM
authors.lastname: Newcomb
authors.forename: Emily S
authors.initials: ES
authors.lastname: Boja
authors.forename: Henry M
authors.initials: HM
authors.lastname: Fales
authors.forename: Joshua
authors.initials: J
authors.lastname: Kaufman
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Stahl
authors.forename: Paul
authors.initials: P
authors.lastname: Wingfield
authors.forename: Robert
authors.initials: R
authors.lastname: Yarchoan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002415:Cats; D002417:Cattle; D019281:Dimerization; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D015967:Gene Expression Regulation, Viral; D016333:HIV Protease / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D012190:Retroviridae / Q000201:enzymology*; D016415:Sequence Alignment
chemical_list: D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease; C079711:HTLV-1 protease