Potent anti-HIV activity of scytovirin domain 1 peptide.
Scytovirin (SVN) is a novel anti-HIV protein isolated from aqueous extracts of the cultured cyanobacterium Scytonema varium. SVN contains two apparent domains, one comprising amino acids 1-48 and the second stretching from amino acids 49 to 95. These two domains display significant homology to each other and a similar pattern of disulfide bonds. Two DNA constructs encoding scytovirin 1-48 (Cys7Ser) (SD1) and 49-95 (Cys55Ser) (SD2) were constructed, and expressed in E. coli, with thioredoxin fused to their N-terminus. Purified recombinant products were tested for binding activities with the HIV surface envelope glycoproteins gp120 and gp41. Whole cell anti-HIV data showed that SD1 had similar anti-HIV activity to the full-length SVN, whereas SD2 had significantly less anti-HIV activity. Further deletion mutants of the SD1 domain (SVN(3-45)Cys7Ser, SVN(6-45)Cys7Ser, SVN(11-45)Cys7Ser) showed that the N-terminal residues are necessary for full anti-HIV activity of SD1 and that an eight amino acid deletion from the C-terminus (SVN(1-40)Cys7Ser) had a significant effect, decreasing the anti-HIV activity of SD1 by approximately five-fold.
Xiong
Changyun
C
Molecular Targets Development Program, National Cancer Institute-Frederick, National Institutes of Health, Bldg 562/Rm 201, Fort Detrick, Frederick, MD 21702, USA.
O'Keefe
Barry R
BR
Byrd
R Andrew
RA
McMahon
James B
JB
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry; D015700:HIV Envelope Protein gp41 / Q000737:chemistry; D037102:Lectins; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D017422:Sequence Analysis, DNA
D019380:Anti-HIV Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D004220:Disulfides; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D037102:Lectins; D008565:Membrane Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; C474342:scytovirin protein, S varium; D004247:DNA