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| | <StructureSection load='2zlf' size='340' side='right'caption='[[2zlf]], [[Resolution|resolution]] 2.59Å' scene=''> | | <StructureSection load='2zlf' size='340' side='right'caption='[[2zlf]], [[Resolution|resolution]] 2.59Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2zlf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZLF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2ZLF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2zlf]] is a 2 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=2ZLF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZLF FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zlg|2zlg]]</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]] 2.59Å</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=2zlf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zlf OCA], [https://pdbe.org/2zlf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zlf RCSB], [https://www.ebi.ac.uk/pdbsum/2zlf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zlf ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2zlf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zlf OCA], [http://pdbe.org/2zlf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zlf RCSB], [http://www.ebi.ac.uk/pdbsum/2zlf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zlf ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 18824]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ribonucleoside-diphosphate reductase]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Cooperman, B S]] | + | [[Category: Cooperman BS]] |
| - | [[Category: Dealwis, C]] | + | [[Category: Dealwis C]] |
| - | [[Category: Fairman, J W]] | + | [[Category: Fairman JW]] |
| - | [[Category: Helmbrecht, E]] | + | [[Category: Helmbrecht E]] |
| - | [[Category: Kreischer, N R]] | + | [[Category: Kreischer NR]] |
| - | [[Category: LaMacchia, J]] | + | [[Category: LaMacchia J]] |
| - | [[Category: Wijerathna, S R]] | + | [[Category: Wijerathna SR]] |
| - | [[Category: Xu, H]] | + | [[Category: Xu H]] |
| - | [[Category: Allosteric enzyme]]
| + | |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Dna replication]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Peptidomimetic inhibition eukaryotic ribonucleotide reductase]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| 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
Eukaryotic ribonucleotide reductase (RR) catalyzes nucleoside diphosphate conversion to deoxynucleoside diphosphate. Crucial for rapidly dividing cells, RR is a target for cancer therapy. RR activity requires formation of a complex between subunits R1 and R2 in which the R2 C-terminal peptide binds to R1. Here we report crystal structures of heterocomplexes containing mammalian R2 C-terminal heptapeptide, P7 (Ac-1FTLDADF7) and its peptidomimetic P6 (1Fmoc(Me)PhgLDChaDF7) bound to Saccharomyces cerevisiae R1 (ScR1). P7 and P6, both of which inhibit ScRR, each bind at two contiguous sites containing residues that are highly conserved among eukaryotes. Such binding is quite distinct from that reported for prokaryotes. The Fmoc group in P6 peptide makes several hydrophobic interactions that contribute to its enhanced potency in binding to ScR1. Combining all of our results, we observe three distinct conformations for peptide binding to ScR1. These structures provide pharmacophores for designing highly potent nonpeptide class I RR inhibitors.
The structural basis for peptidomimetic inhibition of eukaryotic ribonucleotide reductase: a conformationally flexible pharmacophore.,Xu H, Fairman JW, Wijerathna SR, Kreischer NR, LaMacchia J, Helmbrecht E, Cooperman BS, Dealwis C J Med Chem. 2008 Aug 14;51(15):4653-9. Epub 2008 Jul 9. PMID:18610997[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, Fairman JW, Wijerathna SR, Kreischer NR, LaMacchia J, Helmbrecht E, Cooperman BS, Dealwis C. The structural basis for peptidomimetic inhibition of eukaryotic ribonucleotide reductase: a conformationally flexible pharmacophore. J Med Chem. 2008 Aug 14;51(15):4653-9. Epub 2008 Jul 9. PMID:18610997 doi:10.1021/jm800350u
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