Anti-HIV plant proteins catalyze topological changes of DNA into inactive forms.
GAP 31, DAP 32 and DAP 30 comprise a new class of plant proteins with potent anti-HIV activity and insignificant cytotoxicity. We report here the identification and characterization of a new DNA enzyme activity in these three proteins. They irreversibly relax and decatenate supercoiled DNA, as well as catalyze double-stranded breakage to form linear DNA. The relaxed molecules are topologically inactive and no longer serve as substrates for DNA gyrase to form supercoils, phenomena similar to those of cellular topoisomerases in the presence of topoisomerase poisons. The ability of these anti-HIV agents to interrupt essential topological interconversions of DNA may provide a novel mechanism for their antiviral and antitumor actions. The presence of this new DNA topological enzyme activity in these plant proteins also suggests that their anti-HIV activity may not be merely a consequence of ribosome inactivation previously recognized.
Huang
P L
PL
Department of Medicine, Harvard Medical School, Boston, MA 02115.
Chen
H C
HC
Kung
H F
HF
Huang
P L
PL
Huang
P
P
Huang
H I
HI
Lee-Huang
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D004250:DNA Topoisomerases, Type II / Q000737:chemistry; D004278:DNA, Superhelical / Q000187:drug effects; D004331:Drosophila melanogaster; D006678:HIV / Q000187:drug effects*; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000737:chemistry / Q000494:pharmacology*; D054789:Ribosome Inactivating Proteins, Type 1; D017386:Sequence Homology, Amino Acid
D000998:Antiviral Agents; D004278:DNA, Superhelical; C071380:GAP31 protein, Gelonium multiflorum; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D004247:DNA; D004250:DNA Topoisomerases, Type II