3hnf: Difference between revisions
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< | ==Crystal structure of human ribonucleotide reductase 1 bound to the effectors TTP and dATP== | ||
<StructureSection load='3hnf' size='340' side='right'caption='[[3hnf]], [[Resolution|resolution]] 3.16Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3hnf]] 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=3HNF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HNF FirstGlance]. <br> | |||
or | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.16Å</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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</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=3hnf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hnf OCA], [https://pdbe.org/3hnf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hnf RCSB], [https://www.ebi.ac.uk/pdbsum/3hnf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hnf ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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;"> | |||
== 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<ref>PMID:21336276</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3hnf" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
[[ | *[[Ribonucleotide reductase 3D structures|Ribonucleotide reductase 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: Dealwis | __TOC__ | ||
[[Category: Fairman | </StructureSection> | ||
[[Category: Wijerathna | [[Category: Homo sapiens]] | ||
[[Category: Xu | [[Category: Large Structures]] | ||
[[Category: Dealwis CG]] | |||
[[Category: Fairman JW]] | |||
[[Category: Wijerathna SR]] | |||
[[Category: Xu H]] | |||
Latest revision as of 10:24, 6 September 2023
Crystal structure of human ribonucleotide reductase 1 bound to the effectors TTP and dATPCrystal structure of human ribonucleotide reductase 1 bound to the effectors TTP and dATP
Structural highlights
FunctionRIR1_HUMAN Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Publication Abstract from PubMedRibonucleotide 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 AlsoReferences
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