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[[Image:1foz.gif|left|200px]]
{{Seed}}
[[Image:1foz.png|left|200px]]


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{{STRUCTURE_1foz|  PDB=1foz  |  SCENE=  }}  
{{STRUCTURE_1foz|  PDB=1foz  |  SCENE=  }}  


'''STRUCTURE OF CYCLIC PEPTIDE INHIBITORS OF MAMMALIAN RIBONUCLEOTIDE REDUCTASE'''
===STRUCTURE OF CYCLIC PEPTIDE INHIBITORS OF MAMMALIAN RIBONUCLEOTIDE REDUCTASE===




==Overview==
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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.
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{{ABSTRACT_PUBMED_11015199}}


==About this Structure==
==About this Structure==
Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FOZ OCA].  
Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FOZ OCA].  


==Reference==
==Reference==
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[[Category: Ribonucleotide reductase inhibitor]]
[[Category: Ribonucleotide reductase inhibitor]]
[[Category: Transferred no]]
[[Category: Transferred no]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 16:35:40 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 03:42:48 2008''

Revision as of 00:42, 1 July 2008

File:1foz.png

Template:STRUCTURE 1foz

STRUCTURE OF CYCLIC PEPTIDE INHIBITORS OF MAMMALIAN RIBONUCLEOTIDE REDUCTASE

Template:ABSTRACT PUBMED 11015199

About this Structure

Full experimental 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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