Inhibition of the RNA polymerase of vesicular stomatitis virus by ppp5'A2'p5'A and related compounds.
The diadenylate triphosphates ppp5'A2'p5'A and ppp5'A3'p5'A were found to inhibit the purified RNA polymerase ('nucleocapsid') complex from vesicular stomatitis virus (VSV). The corresponding diadenylate monophosphate p5'A2'p5'A did not inhibit, nor did the triadenylate triphosphate ppp5'A2'p5'A2'p5'A; the diadenylate diphosphate pp5'A2'p5'A had intermediate inhibitory activity. Increasing the concentration of ATP, GTP or CTP in the reaction mixture decreased inhibition by ppp5'A2'p5'A, while UTP had minimal or no protective effect. ppp5'A2'p5'A did not protect the RNA polymerase from inactivation by N-ethylmaleimide. This suggests that the action of ppp5'A2'p5'A occurs at a site on the enzyme that is distinct from the N-ethylmaleimide-protecting, ATP-binding site characterized previously.
Subramanian
M
M
Department of Physiology and Biophysics, UMDNJ Robert Wood Johnson Medical School, Rutgers, Piscataway 08854.
Kovacs
T
T
Lesiak
K
K
Torrence
P F
PF
Lenard
J
J
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002213:Capsid; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D007700:Kinetics; D009843:Oligoribonucleotides / Q000494:pharmacology*; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000201:enzymology*; D014758:Viral Core Proteins
D000227:Adenine Nucleotides; D000998:Antiviral Agents; D009843:Oligoribonucleotides; D014758:Viral Core Proteins; C018445:adenosine triphosphate-2',5'-adenosine monophosphate; D012321:DNA-Directed RNA Polymerases; D005033:Ethylmaleimide