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==Crystal structure of the dATP inhibited E. coli class Ia ribonucleotide reductase complex at 4 Angstroms resolution== | ==Crystal structure of the dATP inhibited E. coli class Ia ribonucleotide reductase complex at 4 Angstroms resolution== | ||
<StructureSection load='4erm' size='340' side='right' caption='[[4erm]], [[Resolution|resolution]] 3.95Å' scene=''> | <StructureSection load='4erm' size='340' side='right'caption='[[4erm]], [[Resolution|resolution]] 3.95Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4erm]] is a 8 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4erm]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ERM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ERM FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAT:2-DEOXYADENOSINE-5-DIPHOSPHATE'>DAT</scene>, <scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene>, <scene name='pdbligand=FEO:MU-OXO-DIIRON'>FEO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAT:2-DEOXYADENOSINE-5-DIPHOSPHATE'>DAT</scene>, <scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene>, <scene name='pdbligand=FEO:MU-OXO-DIIRON'>FEO</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=4erm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4erm OCA], [https://pdbe.org/4erm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4erm RCSB], [https://www.ebi.ac.uk/pdbsum/4erm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4erm ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/RIR1_ECOLI RIR1_ECOLI] Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. R1 contains the binding sites for both substrates and allosteric effectors and carries out the actual reduction of the ribonucleotide. It also provides redox-active cysteines. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 23: | Line 20: | ||
==See Also== | ==See Also== | ||
*[[Ribonucleotide reductase|Ribonucleotide reductase]] | *[[Ribonucleotide reductase 3D structures|Ribonucleotide reductase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Escherichia coli K-12]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Drennan | [[Category: Drennan CL]] | ||
[[Category: Zimanyi | [[Category: Zimanyi CM]] | ||
Revision as of 07:10, 7 October 2022
Crystal structure of the dATP inhibited E. coli class Ia ribonucleotide reductase complex at 4 Angstroms resolutionCrystal structure of the dATP inhibited E. coli class Ia ribonucleotide reductase complex at 4 Angstroms resolution
Structural highlights
FunctionRIR1_ECOLI Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. R1 contains the binding sites for both substrates and allosteric effectors and carries out the actual reduction of the ribonucleotide. It also provides redox-active cysteines. Publication Abstract from PubMedRibonucleotide reductases (RNRs) provide the precursors for DNA biosynthesis and repair and are successful targets for anticancer drugs such as clofarabine and gemcitabine. Recently, we reported that dATP inhibits E. coli class Ia RNR by driving formation of RNR subunits into alpha4beta4 rings. Here, we present the first X-ray structure of a gemcitabine-inhibited E. coli RNR and show that the previously described alpha4beta4 rings can interlock to form an unprecedented (alpha4beta4)2 megacomplex. This complex is also seen in a higher-resolution dATP-inhibited RNR structure presented here, which employs a distinct crystal lattice from that observed in the gemcitabine-inhibited case. With few reported examples of protein catenanes, we use data from small-angle X-ray scattering and electron microscopy to both understand the solution conditions that contribute to concatenation in RNRs as well as present a mechanism for the formation of these unusual structures. Tangled up in knots: structures of inactivated forms of E. coli class Ia ribonucleotide reductase.,Zimanyi CM, Ando N, Brignole EJ, Asturias FJ, Stubbe J, Drennan CL Structure. 2012 Aug 8;20(8):1374-83. Epub 2012 Jun 21. PMID:22727814[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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