The effect of synthetic nucleosides and purine analogs on DNA-dependent RNA polymerase

Synthetic nucleosides and purine analogs have been used to study the catalytic activity of DNA-dependent RNA polymerase. The results indicate that the enzyme's catalytic site contains reactive lysine and cysteine residues. A tentative model for the enzyme's catalytic center and explanation of the function of these residues is presented. Kinetic studies indicate that the enzyme's nucleoside triphosphate substrates serve as positive effectors at low substrate concentrations. This may be the first indication that RNA polymerase is an allosteric enzyme. Finally, the periodate oxidation product of methylthioinosine inhibits both a mammalian and bacterial DNA-dependent RNA polymerase. This is the first compound reported to inhibit both enzymes.