Reversible oxidative modification as a mechanism for regulating retroviral protease dimerization and activation.
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.
Davis
David A
DA
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. dadavis@helix.nih.gov
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
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
D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease; C079711:HTLV-1 protease