8p27: Difference between revisions
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The | ==Cryo-EM structure of the anaerobic ribonucleotide reductase from Prevotella copri in its dimeric, dATP-bound state== | ||
<StructureSection load='8p27' size='340' side='right'caption='[[8p27]], [[Resolution|resolution]] 2.73Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8p27]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Prevotella_copri Prevotella copri]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8P27 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8P27 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.73Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8p27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8p27 OCA], [https://pdbe.org/8p27 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8p27 RCSB], [https://www.ebi.ac.uk/pdbsum/8p27 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8p27 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A3E4SF67_9BACT A0A3E4SF67_9BACT] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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 Prevotella copri. 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, P. copri 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 A 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. | |||
Nucleotide binding to the ATP-cone in anaerobic ribonucleotide reductases allosterically regulates activity by modulating substrate binding.,Bimai O, Banerjee I, Rozman Grinberg I, Huang P, Hultgren L, Ekstrom S, Lundin D, Sjoberg BM, Logan DT Elife. 2024 Jul 5;12:RP89292. doi: 10.7554/eLife.89292. PMID:38968292<ref>PMID:38968292</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8p27" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Ribonucleotide reductase 3D structures|Ribonucleotide reductase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Prevotella copri]] | |||
[[Category: Banerjee I]] | |||
[[Category: Bimai O]] | |||
[[Category: Logan DT]] | |||
[[Category: Sjoberg BM]] | |||
Latest revision as of 08:26, 25 September 2024
Cryo-EM structure of the anaerobic ribonucleotide reductase from Prevotella copri in its dimeric, dATP-bound stateCryo-EM structure of the anaerobic ribonucleotide reductase from Prevotella copri in its dimeric, dATP-bound state
Structural highlights
FunctionPublication Abstract from PubMedA 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 Prevotella copri. 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, P. copri 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 A 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. Nucleotide binding to the ATP-cone in anaerobic ribonucleotide reductases allosterically regulates activity by modulating substrate binding.,Bimai O, Banerjee I, Rozman Grinberg I, Huang P, Hultgren L, Ekstrom S, Lundin D, Sjoberg BM, Logan DT Elife. 2024 Jul 5;12:RP89292. doi: 10.7554/eLife.89292. PMID:38968292[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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