EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Nucleotide binding to the ATP-cone in anaerobic ribonucleotide reductases allosterically regulates activity by modulating substrate binding.
ジャーナル・号・ページ	Elife, Vol. 12, Year 2024
掲載日	2024年7月5日
著者	Ornella Bimai / Ipsita Banerjee / Inna Rozman Grinberg / Ping Huang / Lucas Hultgren / Simon Ekström / Daniel Lundin / Britt-Marie Sjöberg / Derek T Logan /
PubMed 要旨	A small, nucleotide-binding domain, the ATP-cone, is found at the N-terminus of most ribonucleotide reductase (RNR) catalytic subunits. By binding adenosine triphosphate (ATP) or deoxyadenosine ...A small, nucleotide-binding domain, the ATP-cone, is found at the N-terminus of most ribonucleotide reductase (RNR) catalytic subunits. By binding adenosine triphosphate (ATP) or deoxyadenosine triphosphate (dATP) it regulates the enzyme activity of all classes of RNR. Functional and structural work on aerobic RNRs has revealed a plethora of ways in which dATP inhibits activity by inducing oligomerisation and preventing a productive radical transfer from one subunit to the active site in the other. Anaerobic RNRs, on the other hand, store a stable glycyl radical next to the active site and the basis for their dATP-dependent inhibition is completely unknown. We present biochemical, biophysical, and structural information on the effects of ATP and dATP binding to the anaerobic RNR from . The enzyme exists in a dimer-tetramer equilibrium biased towards dimers when two ATP molecules are bound to the ATP-cone and tetramers when two dATP molecules are bound. In the presence of ATP, NrdD is active and has a fully ordered glycyl radical domain (GRD) in one monomer of the dimer. Binding of dATP to the ATP-cone results in loss of activity and increased dynamics of the GRD, such that it cannot be detected in the cryo-EM structures. The glycyl radical is formed even in the dATP-bound form, but the substrate does not bind. The structures implicate a complex network of interactions in activity regulation that involve the GRD more than 30 Å away from the dATP molecules, the allosteric substrate specificity site and a conserved but previously unseen flap over the active site. Taken together, the results suggest that dATP inhibition in anaerobic RNRs acts by increasing the flexibility of the flap and GRD, thereby preventing both substrate binding and radical mobilisation.
リンク	Elife / PubMed:38968292 / PubMed Central
手法	EM (単粒子)
解像度	2.4 - 3.17 Å
構造データ	17357 8p23 EMDB-17357, PDB-8p23: Cryo-EM structure of the anaerobic ribonucleotide reductase from Prevotella copri in its dimeric, ATP/CTP-bound state 手法: EM (単粒子) / 解像度: 3.17 Å 17358 8p27 EMDB-17358, PDB-8p27: Cryo-EM structure of the anaerobic ribonucleotide reductase from Prevotella copri in its dimeric, dATP-bound state 手法: EM (単粒子) / 解像度: 2.73 Å 17359 8p28 EMDB-17359, PDB-8p28: Cryo-EM structure of the anaerobic ribonucleotide reductase from Prevotella copri in its tetrameric, dATP-bound state 手法: EM (単粒子) / 解像度: 2.77 Å 17360 8p2c EMDB-17360, PDB-8p2c: Cryo-EM structure of the anaerobic ribonucleotide reductase from Prevotella copri in its tetrameric state produced in the presence of dATP and CTP 手法: EM (単粒子) / 解像度: 2.59 Å 17361 8p2d EMDB-17361, PDB-8p2d: Cryo-EM structure of the dimeric form of the anaerobic ribonucleotide reductase from Prevotella copri produced in the presence of dATP and CTP 手法: EM (単粒子) / 解像度: 2.59 Å 17373 8p2s EMDB-17373, PDB-8p2s: Cryo-EM structure of the anaerobic ribonucleotide reductase from Prevotella copri in its dimeric, ATP/dTTP/GTP-bound state 手法: EM (単粒子) / 解像度: 2.4 Å 17385 8p39 EMDB-17385, PDB-8p39: Cryo-EM structure of the anaerobic ribonucleotide reductase from Prevotella copri in its dimeric, dGTP/ATP-bound state 手法: EM (単粒子) / 解像度: 2.58 Å
化合物	ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子YM ChemComp-CTP: CYTIDINE-5'-TRIPHOSPHATE / CTP ChemComp-ZN: Unknown entry ChemComp-DTP: 2'-DEOXYADENOSINE 5'-TRIPHOSPHATE / dATP ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-TTP: THYMIDINE-5'-TRIPHOSPHATE / dTTP ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP / GTP, エネルギー貯蔵分子YM ChemComp-DGT: 2'-DEOXYGUANOSINE-5'-TRIPHOSPHATE / dGTP
由来	prevotella copri (バクテリア) segatella copri (バクテリア)
キーワード	BIOSYNTHETIC PROTEIN / ribonucleotide reductase glycyl radical enzyme allosteric regulation nucleotide biosynthesis / ribonucleotide reductase / glycyl radical enzyme / allosteric regulation / nucleotide biosynthesis / oxidoreductase