1d5q: Difference between revisions

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[[Image:1d5q.gif|left|200px]]
{{Seed}}
[[Image:1d5q.png|left|200px]]


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{{STRUCTURE_1d5q|  PDB=1d5q  |  SCENE=  }}  
{{STRUCTURE_1d5q|  PDB=1d5q  |  SCENE=  }}  


'''SOLUTION STRUCTURE OF A MINI-PROTEIN REPRODUCING THE CORE OF THE CD4 SURFACE INTERACTING WITH THE HIV-1 ENVELOPE GLYCOPROTEIN'''
===SOLUTION STRUCTURE OF A MINI-PROTEIN REPRODUCING THE CORE OF THE CD4 SURFACE INTERACTING WITH THE HIV-1 ENVELOPE GLYCOPROTEIN===




==Overview==
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Protein-protein interacting surfaces are usually large and intricate, making the rational design of small mimetics of these interfaces a daunting problem. On the basis of a structural similarity between the CDR2-like loop of CD4 and the beta-hairpin region of a short scorpion toxin, scyllatoxin, we transferred the side chains of nine residues of CD4, central in the binding to HIV-1 envelope glycoprotein (gp120), to a structurally homologous region of the scorpion toxin scaffold. In competition experiments, the resulting 27-amino acid miniprotein inhibited binding of CD4 to gp120 with a 40 microM IC(50). Structural analysis by NMR showed that both the backbone of the chimeric beta-hairpin and the introduced side chains adopted conformations similar to those of the parent CD4. Systematic single mutations suggested that most CD4 residues from the CDR2-like loop were reproduced in the miniprotein, including the critical Phe-43. The structural and functional analysis performed suggested five additional mutations that, once incorporated in the miniprotein, increased its affinity for gp120 by 100-fold to an IC(50) of 0.1-1.0 microM, depending on viral strains. The resulting mini-CD4 inhibited infection of CD4(+) cells by different virus isolates. Thus, core regions of large protein-protein interfaces can be reproduced in miniprotein scaffolds, offering possibilities for the development of inhibitors of protein-protein interactions that may represent useful tools in biology and in drug discovery.
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{{ABSTRACT_PUBMED_10557278}}


==About this Structure==
==About this Structure==
Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D5Q OCA].  
Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D5Q OCA].  


==Reference==
==Reference==
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[[Category: Alpha-beta structure]]
[[Category: Alpha-beta structure]]
[[Category: Charybdotoxin-like motif]]
[[Category: Charybdotoxin-like motif]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 13:28:40 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 22:29:02 2008''

Revision as of 19:29, 30 June 2008

File:1d5q.png

Template:STRUCTURE 1d5q

SOLUTION STRUCTURE OF A MINI-PROTEIN REPRODUCING THE CORE OF THE CD4 SURFACE INTERACTING WITH THE HIV-1 ENVELOPE GLYCOPROTEIN

Template:ABSTRACT PUBMED 10557278

About this Structure

Full experimental information is available from OCA.

Reference

Rational engineering of a miniprotein that reproduces the core of the CD4 site interacting with HIV-1 envelope glycoprotein., Vita C, Drakopoulou E, Vizzavona J, Rochette S, Martin L, Menez A, Roumestand C, Yang YS, Ylisastigui L, Benjouad A, Gluckman JC, Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13091-6. PMID:10557278

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