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| | ==Crystal structure of human ribonucleotide reductase 1 bound to the effectors TTP and ATP== | | ==Crystal structure of human ribonucleotide reductase 1 bound to the effectors TTP and ATP== |
| - | <StructureSection load='3hne' size='340' side='right' caption='[[3hne]], [[Resolution|resolution]] 3.11Å' scene=''> | + | <StructureSection load='3hne' size='340' side='right'caption='[[3hne]], [[Resolution|resolution]] 3.11Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3hne]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HNE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HNE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3hne]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HNE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HNE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.11Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hnc|3hnc]], [[3hnd|3hnd]], [[3hnf|3hnf]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RR1, RRM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3hne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hne OCA], [https://pdbe.org/3hne PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hne RCSB], [https://www.ebi.ac.uk/pdbsum/3hne PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hne ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ribonucleoside-diphosphate_reductase Ribonucleoside-diphosphate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.4.1 1.17.4.1] </span></td></tr> | + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3hne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hne OCA], [http://pdbe.org/3hne PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hne RCSB], [http://www.ebi.ac.uk/pdbsum/3hne PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hne ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RIR1_HUMAN RIR1_HUMAN]] Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. | + | [https://www.uniprot.org/uniprot/RIR1_HUMAN RIR1_HUMAN] Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3hne" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3hne" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ribonucleotide reductase 3D structures|Ribonucleotide reductase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Ribonucleoside-diphosphate reductase]] | + | [[Category: Large Structures]] |
| - | [[Category: Dealwis, C G]] | + | [[Category: Dealwis CG]] |
| - | [[Category: Fairman, J W]] | + | [[Category: Fairman JW]] |
| - | [[Category: Wijerathna, S R]] | + | [[Category: Wijerathna SR]] |
| - | [[Category: Xu, H]] | + | [[Category: Xu H]] |
| - | [[Category: Allosteric enzyme]]
| + | |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Dna replication]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Ribonucleotide reductase]]
| + | |
| Structural highlights
Function
RIR1_HUMAN Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
Publication Abstract from PubMed
Ribonucleotide reductase (RR) is an alpha(n)beta(n) (RR1-RR2) complex that maintains balanced dNTP pools by reducing NDPs to dNDPs. RR1 is the catalytic subunit, and RR2 houses the free radical required for catalysis. RR is allosterically regulated by its activator ATP and its inhibitor dATP, which regulate RR activity by inducing oligomerization of RR1. Here, we report the first X-ray structures of human RR1 bound to TTP alone, dATP alone, TTP-GDP, TTP-ATP, and TTP-dATP. These structures provide insights into regulation of RR by ATP or dATP. At physiological dATP concentrations, RR1 forms inactive hexamers. We determined the first X-ray structure of the RR1-dATP hexamer and used single-particle electron microscopy to visualize the alpha(6)-betabeta'-dATP holocomplex. Site-directed mutagenesis and functional assays confirm that hexamerization is a prerequisite for inhibition by dATP. Our data indicate a mechanism for regulating RR activity by dATP-induced oligomerization.
Structural basis for allosteric regulation of human ribonucleotide reductase by nucleotide-induced oligomerization.,Fairman JW, Wijerathna SR, Ahmad MF, Xu H, Nakano R, Jha S, Prendergast J, Welin RM, Flodin S, Roos A, Nordlund P, Li Z, Walz T, Dealwis CG Nat Struct Mol Biol. 2011 Mar;18(3):316-22. Epub 2011 Feb 20. PMID:21336276[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fairman JW, Wijerathna SR, Ahmad MF, Xu H, Nakano R, Jha S, Prendergast J, Welin RM, Flodin S, Roos A, Nordlund P, Li Z, Walz T, Dealwis CG. Structural basis for allosteric regulation of human ribonucleotide reductase by nucleotide-induced oligomerization. Nat Struct Mol Biol. 2011 Mar;18(3):316-22. Epub 2011 Feb 20. PMID:21336276 doi:10.1038/nsmb.2007
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