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2zlg

From Proteopedia

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The Structual Basis for Peptidomimetic Inhibition of Eukaryotic Ribonucleotide Reductase

Structural highlights

2zlg is a 1 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.52Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2zlg"

@@ Line 1: / Line 1: @@
 ==The Structual Basis for Peptidomimetic Inhibition of Eukaryotic Ribonucleotide Reductase==
-<StructureSection load='2zlg' size='340' side='right' caption='[[2zlg]], [[Resolution|resolution]] 2.52&Aring;' scene=''>
+<StructureSection load='2zlg' size='340' side='right'caption='[[2zlg]], [[Resolution|resolution]] 2.52&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2zlg]] is a 1 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=2ZLG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZLG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2zlg]] 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=2ZLG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZLG FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MRT:(5R,9S,12S,15S,18S,21S)-21-BENZYL-12,18-BIS(CARBOXYMETHYL)-15-CYCLOHEXYL-1-(9H-FLUOREN-9-YL)-4-METHYL-9-(2-METHYLPROPYL)-3,6,10,13,16,19-HEXAOXO-5-PHENYL-2-OXA-4,8,11,14,17,20-HEXAAZADOCOSAN-22-OIC+ACID'>MRT</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]] 2.52&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zlf|2zlf]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MRT:(5R,9S,12S,15S,18S,21S)-21-BENZYL-12,18-BIS(CARBOXYMETHYL)-15-CYCLOHEXYL-1-(9H-FLUOREN-9-YL)-4-METHYL-9-(2-METHYLPROPYL)-3,6,10,13,16,19-HEXAOXO-5-PHENYL-2-OXA-4,8,11,14,17,20-HEXAAZADOCOSAN-22-OIC+ACID'>MRT</scene></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=2zlg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zlg OCA], [https://pdbe.org/2zlg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zlg RCSB], [https://www.ebi.ac.uk/pdbsum/2zlg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zlg 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=2zlg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zlg OCA], [http://pdbe.org/2zlg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zlg RCSB], [http://www.ebi.ac.uk/pdbsum/2zlg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zlg ProSAT]</span></td></tr>
 </table>
 == 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 ==
 [[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/zl/2zlg_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zl/2zlg_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 32: / Line 31: @@
 ==See Also==
-*[[Ribonucleotide reductase|Ribonucleotide reductase]]
+*[[Ribonucleotide reductase 3D structures|Ribonucleotide reductase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Atcc 18824]]
+[[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: Dna replication]]
-[[Category: Nucleotide-binding]]
-[[Category: Oxidoreductase]]
-[[Category: Peptidomimetic inhibition eukaryotic ribonucleotide reductase]]
-[[Category: Phosphoprotein]]

2zlg

From Proteopedia

Current revision

The Structual Basis for Peptidomimetic Inhibition of Eukaryotic Ribonucleotide Reductase

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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