Inhibition of simian virus 40 DNA replication by specific modification of T-antigen with oxidized ATP.
We covalently bound periodate-oxidized ATP (oATP) to purified simian virus 40 (SV40) large T-antigen and determined the effect of this modification on viral DNA replication and three other biochemical activities of T-antigen. The oATP bound specifically to T-antigen, inhibiting the ATPase activity and preventing T-antigen from activating SV40 DNA replication in vitro. In contrast, binding of oATP had no effect on the DNA-binding activity of T-antigen nor on its ability to form a complex with DNA polymerase alpha. These results provide direct biochemical evidence suggesting that the T-antigen ATPase activity is necessary for viral DNA replication.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000952:Antigens, Polyomavirus Transforming; D000957:Antigens, Viral, Tumor / Q000037:antagonists & inhibitors*; D004261:DNA Replication / Q000187:drug effects*; D006825:Hybridomas; D007700:Kinetics; D009856:Oncogene Proteins, Viral / Q000037:antagonists & inhibitors*; D011494:Protein Kinases / Q000378:metabolism*; D013539:Simian virus 40 / Q000187:drug effects / Q000235:genetics*; D013698:Templates, Genetic
D000952:Antigens, Polyomavirus Transforming; D000957:Antigens, Viral, Tumor; D009856:Oncogene Proteins, Viral; C004282:periodate-oxidized adenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D000251:Adenosine Triphosphatases