title: 2'-Deoxy-2'-azidoadenosine triphosphate and 2'-deoxy-2'-fluoroadenosine triphosphate as substrates and inhibitors for Escherichia coli DNA-dependent RNA polymerase.
abstract: The effects of 2'-substitutions of ATP on the substrate and inhibitor properties for RNA synthesis were studied in the poly(dAT)-dependent reaction of Escherichia coli RNA polymerase. In the presence of UTP, 2'-deoxy-2'-azidoadenosine 5'-triphosphate (AZTP) was incorporated into an acid-insoluble fraction at one-tenth of the rate of ATP incorporation; it thus acts as a competitive inhibitor for poly(AU) synthesis. On the other hand, another ATP analog, 2'-deoxy-2'-fluoroadenosine 5'-triphosphate (AfTP), was co-polymerized with UTP into acid-insoluble materials at a rate less than 1% of that of ATP incorporation; in addition, it exerted a strong but mixed-type inhibition on poly(AU) synthesis. Different modes of action of the two ATP analogs are discussed in connection with the specificity of substrate recognition by RNA polymerase.
mesh_terms: D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003838:Deoxyadenine Nucleotides; D003839:Deoxyadenosines / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology*; D011485:Protein Binding; D012329:RNA, Bacterial / Q000096:biosynthesis; D013379:Substrate Specificity
chemical_list: D003838:Deoxyadenine Nucleotides; D003839:Deoxyadenosines; D012329:RNA, Bacterial; C025663:2'-deoxy-2'-azidoadenosine triphosphate; C025664:2'-fluoro-2'-deoxyadenosine triphosphate; D012321:DNA-Directed RNA Polymerases