How ATP and dATP reposition class III ribonucleotide reductase cone domains to regulate enzyme activity.

ABSTRACT: Ribonucleotide reductases (RNRs) catalyze the conversion of ribonucleotides to deoxyribonucleotides. In the majority of cases, RNR activity is allosterically regulated by the cellular 2'-deoxyadenosine 5'-triphosphate (dATP)/adenosine 5'-triphosphate (ATP) ratio. To investigate allosteric activity regulation in anaerobic or class III (glycyl radical containing) RNRs, we determine cryo-electron microscopy structures of the class III RNR from Streptococcus thermophilus (StNrdD). We find that StNrdD's regulatory "cone" domains adopt markedly different conformations depending on whether the activator ATP or the inhibitor dATP is bound and that these different conformations alternatively position an "active site flap" toward the active site (ATP-bound) or away (dATP-bound). In contrast,

SUBMITTER: Andree GA 

PROVIDER: S-EPMC12662201 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature