1d5q
From Proteopedia
| Line 7: | Line 7: | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1cdh|1CDH]], [[1scy|1SCY]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1d5q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d5q OCA], [http://www.ebi.ac.uk/pdbsum/1d5q PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1d5q RCSB]</span> | ||
}} | }} | ||
| Line 35: | Line 38: | ||
[[Category: charybdotoxin-like motif]] | [[Category: charybdotoxin-like motif]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:35:09 2008'' |
Revision as of 16:35, 30 March 2008
| |||||||
| Related: | 1CDH, 1SCY
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
SOLUTION STRUCTURE OF A MINI-PROTEIN REPRODUCING THE CORE OF THE CD4 SURFACE INTERACTING WITH THE HIV-1 ENVELOPE GLYCOPROTEIN
Overview
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.
About this Structure
1D5Q is a Protein complex structure of sequences from [1]. Full crystallographic 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
Page seeded by OCA on Sun Mar 30 19:35:09 2008
