2jp5: Difference between revisions

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[[Image:2jp5.jpg|left|200px]]
{{Seed}}
[[Image:2jp5.png|left|200px]]


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{{STRUCTURE_2jp5|  PDB=2jp5  |  SCENE=  }}  
{{STRUCTURE_2jp5|  PDB=2jp5  |  SCENE=  }}  


'''ATWLPPR an anti-angiogenic peptide'''
===ATWLPPR an anti-angiogenic peptide===




==Overview==
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Heptapeptide ATWLPPR (A7R), identified in our laboratory by screening a mutated phage library, was shown to bind specifically to neuropilin-1 (NRP-1) and then to selectively inhibit VEGF(165) binding to this receptor. In vivo, treatment with A7R resulted in decreasing breast cancer angiogenesis and growth. The present work is focused on structural characterization of A7R. Analogs of the peptide, obtained by substitution of each amino acid with alanine (alanine-scanning) or by amino acid deletion, have been systematically assayed to determine the relative importance of the side chains of each residue with respect to the inhibitory effect of A7R on VEGF(165) binding to NRP-1. We show here the importance of the C-terminal sequence LPPR and particularly the key role of C-terminal arginine. In solution, A7R displays significant secondary structure of the backbone adopting an extended conformation. However, the functional groups of arginine are very flexible in the absence of NRP-1 pointing to an induced fit upon binding to the receptor. A MD trajectory of the A7R/NRP-1 complex in explicit water, based on the recent tuftsin/NRP-1 crystal structure, has revealed the hydrogen-bonding network that contributes to A7R's binding activity.
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{{ABSTRACT_PUBMED_17983687}}


==About this Structure==
==About this Structure==
Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JP5 OCA].  
Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JP5 OCA].  


==Reference==
==Reference==
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[[Category: Peptide]]
[[Category: Peptide]]
[[Category: Protein binding inhibitor]]
[[Category: Protein binding inhibitor]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 09:08:21 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 03:38:44 2008''

Revision as of 00:38, 29 July 2008

File:2jp5.png

Template:STRUCTURE 2jp5

ATWLPPR an anti-angiogenic peptide

Template:ABSTRACT PUBMED 17983687

About this Structure

Full experimental information is available from OCA.

Reference

Structure-function analysis of the antiangiogenic ATWLPPR peptide inhibiting VEGF(165) binding to neuropilin-1 and molecular dynamics simulations of the ATWLPPR/neuropilin-1 complex., Starzec A, Ladam P, Vassy R, Badache S, Bouchemal N, Navaza A, du Penhoat CH, Perret GY, Peptides. 2007 Dec;28(12):2397-402. Epub 2007 Sep 29. PMID:17983687

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