1foz
From Proteopedia
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| - | [[Image:1foz.gif|left|200px]] | ||
| - | + | ==STRUCTURE OF CYCLIC PEPTIDE INHIBITORS OF MAMMALIAN RIBONUCLEOTIDE REDUCTASE== | |
| - | + | <StructureSection load='1foz' size='340' side='right'caption='[[1foz]]' scene=''> | |
| - | + | == Structural highlights == | |
| - | | | + | <table><tr><td colspan='2'>[[1foz]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FOZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FOZ FirstGlance]. <br> |
| - | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></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=1foz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1foz OCA], [https://pdbe.org/1foz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1foz RCSB], [https://www.ebi.ac.uk/pdbsum/1foz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1foz ProSAT]</span></td></tr> | |
| - | + | </table> | |
| - | + | <div style="background-color:#fffaf0;"> | |
| - | ''' | + | == Publication Abstract from PubMed == |
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Mammalian ribonucleotide reductase (mRR), a potential target for cancer intervention, is composed of two subunits, mR1 and mR2, whose association is critical for enzyme activity. In this article we describe the structural features of the mRR-inhibitor Ac-F-c[ELAK]-DF (Peptide 3) while bound to the mR1 subunit as determined by transferred NOEs. Peptide 3 is a cyclic analogue of the N-acetylated form of the heptapeptide C-terminus of the mR2 subunit (Ac-FTLDADF), which is the link between the two subunits and previously shown to be the minimal sequence inhibitor mRR by competing with mR2 for binding to mR1. Structural refinement employing an ensemble-based, full-relaxation matrix approach resulted in two structures varying in the conformations of F(1) and the cyclic lactam side chains of E(2) and K(5). The remainder of the molecule, both backbone and side chains, is extremely well-defined, with an RMSD of 0.54 A. The structural features of this conformationally constrained analogue provide unique insight into the requirements for binding to mR1, critical for further inhibitor development. | Mammalian ribonucleotide reductase (mRR), a potential target for cancer intervention, is composed of two subunits, mR1 and mR2, whose association is critical for enzyme activity. In this article we describe the structural features of the mRR-inhibitor Ac-F-c[ELAK]-DF (Peptide 3) while bound to the mR1 subunit as determined by transferred NOEs. Peptide 3 is a cyclic analogue of the N-acetylated form of the heptapeptide C-terminus of the mR2 subunit (Ac-FTLDADF), which is the link between the two subunits and previously shown to be the minimal sequence inhibitor mRR by competing with mR2 for binding to mR1. Structural refinement employing an ensemble-based, full-relaxation matrix approach resulted in two structures varying in the conformations of F(1) and the cyclic lactam side chains of E(2) and K(5). The remainder of the molecule, both backbone and side chains, is extremely well-defined, with an RMSD of 0.54 A. The structural features of this conformationally constrained analogue provide unique insight into the requirements for binding to mR1, critical for further inhibitor development. | ||
| - | + | Structure-based optimization of peptide inhibitors of mammalian ribonucleotide reductase.,Pellegrini M, Liehr S, Fisher AL, Laub PB, Cooperman BS, Mierke DF Biochemistry. 2000 Oct 10;39(40):12210-5. PMID:11015199<ref>PMID:11015199</ref> | |
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| - | Structure-based optimization of peptide inhibitors of mammalian ribonucleotide reductase., Pellegrini M, Liehr S, Fisher AL, Laub PB, Cooperman BS, Mierke DF | + | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 1foz" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Cooperman BS]] | ||
| + | [[Category: Fisher AL]] | ||
| + | [[Category: Liehr S]] | ||
| + | [[Category: Mierke DF]] | ||
| + | [[Category: Pellegrini M]] | ||
Current revision
STRUCTURE OF CYCLIC PEPTIDE INHIBITORS OF MAMMALIAN RIBONUCLEOTIDE REDUCTASE
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