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2zlg
From Proteopedia
(Difference between revisions)
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| - | [[ | + | ==The Structual Basis for Peptidomimetic Inhibition of Eukaryotic Ribonucleotide Reductase== |
| + | <StructureSection load='2zlg' size='340' side='right' caption='[[2zlg]], [[Resolution|resolution]] 2.52Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2zlg]] is a 1 chain structure with 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=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> | ||
| + | </td></tr><tr><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><br> | ||
| + | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zlf|2zlf]]</td></tr> | ||
| + | <tr><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><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://www.rcsb.org/pdb/explore.do?structureId=2zlg RCSB], [http://www.ebi.ac.uk/pdbsum/2zlg PDBsum]</span></td></tr> | ||
| + | <table> | ||
| + | == 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> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:18610997</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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| - | + | ||
==See Also== | ==See Also== | ||
*[[Ribonucleotide reductase|Ribonucleotide reductase]] | *[[Ribonucleotide reductase|Ribonucleotide reductase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Ribonucleoside-diphosphate reductase]] | [[Category: Ribonucleoside-diphosphate reductase]] | ||
[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
Revision as of 10:01, 29 September 2014
The Structual Basis for Peptidomimetic Inhibition of Eukaryotic Ribonucleotide Reductase
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Categories: Ribonucleoside-diphosphate reductase | Saccharomyces cerevisiae | Cooperman, B S. | Dealwis, C. | Fairman, J W. | Helmbrecht, E. | Kreischer, N R. | LaMacchia, J. | Wijerathna, S R. | Xu, H. | Allosteric enzyme | Atp-binding | Dna replication | Nucleotide-binding | Oxidoreductase | Peptidomimetic inhibition eukaryotic ribonucleotide reductase | Phosphoprotein
