1foz
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(New page: 200px<br /><applet load="1foz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1foz" /> '''STRUCTURE OF CYCLIC PEPTIDE INHIBITORS OF MA...)
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Revision as of 22:02, 24 November 2007
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STRUCTURE OF CYCLIC PEPTIDE INHIBITORS OF MAMMALIAN RIBONUCLEOTIDE REDUCTASE
Overview
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.
About this Structure
1FOZ is a Protein complex structure of sequences from [1] with ACE as ligand. Full crystallographic information is available from OCA.
Reference
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
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