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| | <StructureSection load='5d1y' size='340' side='right'caption='[[5d1y]], [[Resolution|resolution]] 9.01Å' scene=''> | | <StructureSection load='5d1y' size='340' side='right'caption='[[5d1y]], [[Resolution|resolution]] 9.01Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5d1y]] 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=5D1Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5D1Y FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5d1y]] 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=5D1Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5D1Y FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RRM1, RR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 9.005Å</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'>[https://proteopedia.org/fgij/fg.htm?mol=5d1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d1y OCA], [https://pdbe.org/5d1y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5d1y RCSB], [https://www.ebi.ac.uk/pdbsum/5d1y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5d1y ProSAT]</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=5d1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d1y OCA], [http://pdbe.org/5d1y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5d1y RCSB], [http://www.ebi.ac.uk/pdbsum/5d1y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5d1y 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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| | | | |
| | ==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: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ribonucleoside-diphosphate reductase]]
| + | [[Category: Ando N]] |
| - | [[Category: Ando, N]] | + | [[Category: Asturias F]] |
| - | [[Category: Asturias, F]] | + | [[Category: Brignole EJ]] |
| - | [[Category: Brignole, E J]] | + | [[Category: Drennan CL]] |
| - | [[Category: Drennan, C L]] | + | [[Category: Li H]] |
| - | [[Category: Li, H]] | + | [[Category: McLaughlin MI]] |
| - | [[Category: McLaughlin, M I]] | + | [[Category: Page J]] |
| - | [[Category: Page, J]] | + | [[Category: Stubbe J]] |
| - | [[Category: Stubbe, J]] | + | [[Category: Thompson S]] |
| - | [[Category: Thompson, S]] | + | |
| - | [[Category: Atp cone]]
| + | |
| - | [[Category: Deoxyribonucleotide]]
| + | |
| - | [[Category: Oligomerization]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| 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 reductases (RNRs) are responsible for all de novo biosynthesis of DNA precursors in nature by catalyzing the conversion of ribonucleotides to deoxyribonucleotides. Because of its essential role in cell division, human RNR is a target for a number of anticancer drugs in clinical use. Like other class Ia RNRs, human RNR requires both a radical-generation subunit (beta) and nucleotide-binding subunit (alpha) for activity. Because of their complex dependence on allosteric effectors, however, the active and inactive quaternary forms of many class Ia RNRs have remained in question. Here, we present an X-ray crystal structure of the human alpha subunit in the presence of inhibiting levels of dATP, depicting a ring-shaped hexamer (alpha6) where the active sites line the inner hole. Surprisingly, our small-angle X-ray scattering (SAXS) results indicate that human alpha forms a similar hexamer in the presence of ATP, an activating effector. In both cases, alpha6 is assembled from dimers (alpha2) without a previously proposed tetramer intermediate (alpha4). However, we show with SAXS and electron microscopy that at millimolar ATP, the ATP-induced alpha6 can further interconvert with higher-order filaments. Differences in the dATP- and ATP-induced alpha6 were further examined by SAXS in the presence of the beta subunit and by activity assays as a function of ATP or dATP. Together, these results suggest that dATP-induced alpha6 is more stable than the ATP-induced alpha6 and that stabilization of this ring-shaped configuration provides a mechanism to prevent access of the beta subunit to the active site of alpha.
Allosteric Inhibition of Human Ribonucleotide Reductase by dATP Entails the Stabilization of a Hexamer.,Ando N, Li H, Brignole EJ, Thompson S, McLaughlin MI, Page JE, Asturias FJ, Stubbe J, Drennan CL Biochemistry. 2016 Jan 19;55(2):373-81. doi: 10.1021/acs.biochem.5b01207. Epub, 2016 Jan 4. PMID:26727048[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ando N, Li H, Brignole EJ, Thompson S, McLaughlin MI, Page JE, Asturias FJ, Stubbe J, Drennan CL. Allosteric Inhibition of Human Ribonucleotide Reductase by dATP Entails the Stabilization of a Hexamer. Biochemistry. 2016 Jan 19;55(2):373-81. doi: 10.1021/acs.biochem.5b01207. Epub, 2016 Jan 4. PMID:26727048 doi:http://dx.doi.org/10.1021/acs.biochem.5b01207
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