Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Nucleotide binding to the ATP-cone in anaerobic ribonucleotide reductases allosterically regulates activity by modulating substrate binding.
Journal, issue, pages	Elife, Vol. 12, Year 2024
Publish date	Jul 5, 2024
Authors	Ornella Bimai / Ipsita Banerjee / Inna Rozman Grinberg / Ping Huang / Lucas Hultgren / Simon Ekström / Daniel Lundin / Britt-Marie Sjöberg / Derek T Logan /
PubMed Abstract	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.
External links	Elife / PubMed:38968292 / PubMed Central
Methods	EM (single particle)
Resolution	2.4 - 3.17 Å
Structure data	17357 8p23 EMDB-17357, PDB-8p23: Cryo-EM structure of the anaerobic ribonucleotide reductase from Prevotella copri in its dimeric, ATP/CTP-bound state Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 2.58 Å
Chemicals	ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying moleculeYM ChemComp-CTP: CYTIDINE-5'-TRIPHOSPHATE ChemComp-ZN: Unknown entry ChemComp-DTP: 2'-DEOXYADENOSINE 5'-TRIPHOSPHATE ChemComp-MG: Unknown entry ChemComp-TTP: THYMIDINE-5'-TRIPHOSPHATE ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying moleculeYM ChemComp-DGT: 2'-DEOXYGUANOSINE-5'-TRIPHOSPHATE
Source	prevotella copri (bacteria) segatella copri (bacteria)
Keywords	BIOSYNTHETIC PROTEIN / ribonucleotide reductase glycyl radical enzyme allosteric regulation nucleotide biosynthesis / ribonucleotide reductase / glycyl radical enzyme / allosteric regulation / nucleotide biosynthesis / oxidoreductase