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| - | [[Image:2cvs.gif|left|200px]] | |
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| - | {{Structure
| + | ==Structures of Yeast Ribonucleotide Reductase I== |
| - | |PDB= 2cvs |SIZE=350|CAPTION= <scene name='initialview01'>2cvs</scene>, resolution 2.60Å
| + | <StructureSection load='2cvs' size='340' side='right'caption='[[2cvs]], [[Resolution|resolution]] 2.60Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND=
| + | <table><tr><td colspan='2'>[[2cvs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CVS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CVS FirstGlance]. <br> |
| - | |ACTIVITY= [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]
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> |
| - | |GENE= | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2cvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cvs OCA], [https://pdbe.org/2cvs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cvs RCSB], [https://www.ebi.ac.uk/pdbsum/2cvs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cvs ProSAT]</span></td></tr> |
| - | }}
| + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/RIR1_YEAST RIR1_YEAST] Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.<ref>PMID:11893751</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cv/2cvs_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2cvs ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Ribonucleotide reductase catalyzes a crucial step in de novo DNA synthesis and is allosterically controlled by relative levels of dNTPs to maintain a balanced pool of deoxynucleoside triphosphates in the cell. In eukaryotes, the enzyme comprises a heterooligomer of alpha(2) and beta(2) subunits. The alpha subunit, Rnr1, contains catalytic and regulatory sites. Here, we report the only x-ray structures of the eukaryotic alpha subunit of ribonucleotide reductase from Saccharomyces cerevisiae. The structures of the apo-, AMPPNP only-, AMPPNP-CDP-, AMPPNP-UDP-, dGTP-ADP- and TTP-GDP-bound complexes give insight into substrate and effector binding and specificity cross-talk. These are Class I structures with the only fully ordered catalytic sites, including loop 2, a stretch of polypeptide that spans specificity and catalytic sites, conferring specificity. Binding of specificity effector rearranges loop 2; in our structures, this rearrangement moves P294, a residue unique to eukaryotes, out of the catalytic site, accommodating substrate binding. Substrate binding further rearranges loop 2. Cross-talk, by which effector binding regulates substrate preference, occurs largely through R293 and Q288 of loop 2, which are analogous to residues in Thermotoga maritima that mediate cross-talk. However loop-2 conformations and residue-substrate interactions differ substantially between yeast and T. maritima. In most effector-substrate complexes, water molecules help mediate substrate-loop 2 interactions. Finally, the substrate ribose binds with its 3' hydroxyl closer than its 2' hydroxyl to C218 of the catalytic redox pair. We also see a conserved water molecule at the catalytic site in all our structures, near the ribose 2' hydroxyl. |
| | | | |
| - | '''Structures of Yeast Ribonucleotide Reductase I'''
| + | Structures of eukaryotic ribonucleotide reductase I provide insights into dNTP regulation.,Xu H, Faber C, Uchiki T, Fairman JW, Racca J, Dealwis C Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4022-7. Epub 2006 Mar 6. PMID:16537479<ref>PMID:16537479</ref> |
| | | | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 2cvs" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Overview== | + | ==See Also== |
| - | Ribonucleotide reductase catalyzes a crucial step in de novo DNA synthesis and is allosterically controlled by relative levels of dNTPs to maintain a balanced pool of deoxynucleoside triphosphates in the cell. In eukaryotes, the enzyme comprises a heterooligomer of alpha(2) and beta(2) subunits. The alpha subunit, Rnr1, contains catalytic and regulatory sites. Here, we report the only x-ray structures of the eukaryotic alpha subunit of ribonucleotide reductase from Saccharomyces cerevisiae. The structures of the apo-, AMPPNP only-, AMPPNP-CDP-, AMPPNP-UDP-, dGTP-ADP- and TTP-GDP-bound complexes give insight into substrate and effector binding and specificity cross-talk. These are Class I structures with the only fully ordered catalytic sites, including loop 2, a stretch of polypeptide that spans specificity and catalytic sites, conferring specificity. Binding of specificity effector rearranges loop 2; in our structures, this rearrangement moves P294, a residue unique to eukaryotes, out of the catalytic site, accommodating substrate binding. Substrate binding further rearranges loop 2. Cross-talk, by which effector binding regulates substrate preference, occurs largely through R293 and Q288 of loop 2, which are analogous to residues in Thermotoga maritima that mediate cross-talk. However loop-2 conformations and residue-substrate interactions differ substantially between yeast and T. maritima. In most effector-substrate complexes, water molecules help mediate substrate-loop 2 interactions. Finally, the substrate ribose binds with its 3' hydroxyl closer than its 2' hydroxyl to C218 of the catalytic redox pair. We also see a conserved water molecule at the catalytic site in all our structures, near the ribose 2' hydroxyl. | + | *[[Ribonucleotide reductase 3D structures|Ribonucleotide reductase 3D structures]] |
| - | | + | == References == |
| - | ==About this Structure== | + | <references/> |
| - | 2CVS is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CVS OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference==
| + | [[Category: Large Structures]] |
| - | Structures of eukaryotic ribonucleotide reductase I provide insights into dNTP regulation., Xu H, Faber C, Uchiki T, Fairman JW, Racca J, Dealwis C, Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4022-7. Epub 2006 Mar 6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16537479 16537479]
| + | |
| - | [[Category: Ribonucleoside-diphosphate reductase]] | + | |
| | [[Category: Saccharomyces cerevisiae]] | | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Single protein]]
| + | [[Category: Dealwis C]] |
| - | [[Category: Dealwis, C.]] | + | [[Category: Faber C]] |
| - | [[Category: Faber, C.]] | + | [[Category: Fairman JW]] |
| - | [[Category: Fairman, J W.]] | + | [[Category: Racca J]] |
| - | [[Category: Racca, J.]] | + | [[Category: Uchiki T]] |
| - | [[Category: Uchiki, T.]] | + | [[Category: Xu H]] |
| - | [[Category: Xu, H.]] | + | |
| - | [[Category: dntp regulation]]
| + | |
| - | [[Category: eukaryotic]]
| + | |
| - | [[Category: ribonucleotide reductase]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:20:19 2008''
| + | |
| Structural highlights
Function
RIR1_YEAST Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Ribonucleotide reductase catalyzes a crucial step in de novo DNA synthesis and is allosterically controlled by relative levels of dNTPs to maintain a balanced pool of deoxynucleoside triphosphates in the cell. In eukaryotes, the enzyme comprises a heterooligomer of alpha(2) and beta(2) subunits. The alpha subunit, Rnr1, contains catalytic and regulatory sites. Here, we report the only x-ray structures of the eukaryotic alpha subunit of ribonucleotide reductase from Saccharomyces cerevisiae. The structures of the apo-, AMPPNP only-, AMPPNP-CDP-, AMPPNP-UDP-, dGTP-ADP- and TTP-GDP-bound complexes give insight into substrate and effector binding and specificity cross-talk. These are Class I structures with the only fully ordered catalytic sites, including loop 2, a stretch of polypeptide that spans specificity and catalytic sites, conferring specificity. Binding of specificity effector rearranges loop 2; in our structures, this rearrangement moves P294, a residue unique to eukaryotes, out of the catalytic site, accommodating substrate binding. Substrate binding further rearranges loop 2. Cross-talk, by which effector binding regulates substrate preference, occurs largely through R293 and Q288 of loop 2, which are analogous to residues in Thermotoga maritima that mediate cross-talk. However loop-2 conformations and residue-substrate interactions differ substantially between yeast and T. maritima. In most effector-substrate complexes, water molecules help mediate substrate-loop 2 interactions. Finally, the substrate ribose binds with its 3' hydroxyl closer than its 2' hydroxyl to C218 of the catalytic redox pair. We also see a conserved water molecule at the catalytic site in all our structures, near the ribose 2' hydroxyl.
Structures of eukaryotic ribonucleotide reductase I provide insights into dNTP regulation.,Xu H, Faber C, Uchiki T, Fairman JW, Racca J, Dealwis C Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4022-7. Epub 2006 Mar 6. PMID:16537479[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Domkin V, Thelander L, Chabes A. Yeast DNA damage-inducible Rnr3 has a very low catalytic activity strongly stimulated after the formation of a cross-talking Rnr1/Rnr3 complex. J Biol Chem. 2002 May 24;277(21):18574-8. Epub 2002 Mar 13. PMID:11893751 doi:http://dx.doi.org/10.1074/jbc.M201553200
- ↑ Xu H, Faber C, Uchiki T, Fairman JW, Racca J, Dealwis C. Structures of eukaryotic ribonucleotide reductase I provide insights into dNTP regulation. Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4022-7. Epub 2006 Mar 6. PMID:16537479
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