Teie Journal of Riological Chemistry

The structural requirements for reactivity at the substrate site and for interaction at the regulatory site of ribonucleotide reductase from Lacfobacillus leichmannii have been studied with the use of several nucleotide antibiotics. The 5’4riphosphates of tubercidin, toyocamycin, and sangivamycin were substrates. Without Mg++, tubercidin 5’triphosphate was a better substrate than ATP. Therefore, the imidazole ring of ATP can be replaced by the pyrrole ring. The presence of a hydroxyl group at position 3’ is especially important for reduction since 3’-deoxyadenosine 5’-triphosphate was not a substrate. 3’-Deoxyadenosine 5’-triphosphate did inhibit reduction of ATP but did not compete for the reduction of UTP, GTP, or CTP. Modification of the reductase by the “prime effecters,” dGTP and 2’-dATP, stimulated the reduction of the 5’triphosphates of tubercidin and toyocamycin. Reduction of sangivamycin 5’4riphosphate was stimulated by dGTP but not 2’-dATP. Although 3’-deoxyadenosine 5’4riphosphate was not a substrate, it was 50% as good an effector as 2’dATP for stimulating the reduction of CTP. The pyrrolopyrimidine ribonucleotide antibiotics were less effective than 3’-deoxyadenosine 5’4riphosphate and the pyrazolopyrimidine ribonucleotide, formycin 5’-triphosphate, could not be substituted for ATP. Carbon atom 8 and nitrogen atom 9 of the base portion of ATP, but not nitrogen atom 7, are important for interaction at the regulatory site of ribo-