9DCA

S. thermophilus class III ribonucleotide reductase with ATP and TTP

9DCA の概要

• エントリーDOI: 10.2210/pdb9dca/pdb
• 関連するPDBエントリー: 9D3X 9DAU
• EMDBエントリー: 46747
• 分子名称: Anaerobic ribonucleoside-triphosphate reductase, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: ribonucleotide reductase, allosteric regulation, cone domain, glycyl radical enzyme, oxidoreductase
• 由来する生物種: Streptococcus thermophilus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 170282.71

構造登録者

Andree, G.A.,Drennan, C.L. (登録日: 2024-08-25, 公開日: 2025-12-17, 最終更新日: 2025-12-24)

主引用文献

Andree, G.A.,Miller-Brown, K.R.,Zhao, Z.,Smith, A.K.,Dawson, C.D.,Deredge, D.J.,Drennan, C.L.
How ATP and dATP reposition class III ribonucleotide reductase cone domains to regulate enzyme activity.
Sci Adv, 11:eady9156-eady9156, 2025

PubMed 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 (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, the position of the glycyl radical domain is unaffected by the cone domain conformations, suggesting that StNrdD activity is regulated through control of substrate binding rather than control of radical transfer. Hydrogen-deuterium exchange mass spectrometry and mutagenesis support the structural findings. In addition, our structural data provide insight into the molecular basis by which ATP and dATP binding lead to the observed differential cone domain conformations.

PubMed: 41313771
DOI: 10.1126/sciadv.ady9156

実験手法

ELECTRON MICROSCOPY (3.6 Å)