1d5q: Difference between revisions

From Proteopedia
Jump to navigationJump to search
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
New page: left|200px<br /> <applet load="1d5q" size="450" color="white" frame="true" align="right" spinBox="true" caption="1d5q" /> '''SOLUTION STRUCTURE OF A MINI-PROTEIN REPROD...
 
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
 
(14 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:1d5q.gif|left|200px]]<br />
<applet load="1d5q" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1d5q" />
'''SOLUTION STRUCTURE OF A MINI-PROTEIN REPRODUCING THE CORE OF THE CD4 SURFACE INTERACTING WITH THE HIV-1 ENVELOPE GLYCOPROTEIN'''<br />


==Overview==
==SOLUTION STRUCTURE OF A MINI-PROTEIN REPRODUCING THE CORE OF THE CD4 SURFACE INTERACTING WITH THE HIV-1 ENVELOPE GLYCOPROTEIN==
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.
<StructureSection load='1d5q' size='340' side='right'caption='[[1d5q]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1d5q]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D5Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1D5Q FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 1 model</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1d5q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d5q OCA], [https://pdbe.org/1d5q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1d5q RCSB], [https://www.ebi.ac.uk/pdbsum/1d5q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1d5q ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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==
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<ref>PMID:10557278</ref>
1D5Q is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1D5Q OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10557278 10557278]
</div>
[[Category: Protein complex]]
<div class="pdbe-citations 1d5q" style="background-color:#fffaf0;"></div>
[[Category: Benjouad, A.]]
== References ==
[[Category: Drakopoulou, E.]]
<references/>
[[Category: Gluckman, J.C.]]
__TOC__
[[Category: Martin, L.]]
</StructureSection>
[[Category: Menez, A.]]
[[Category: Large Structures]]
[[Category: Rochette, S.]]
[[Category: Benjouad A]]
[[Category: Roumestand, C.]]
[[Category: Drakopoulou E]]
[[Category: Vita, C.]]
[[Category: Gluckman JC]]
[[Category: Vizzanova, J.]]
[[Category: Martin L]]
[[Category: Yang, Y.S.]]
[[Category: Menez A]]
[[Category: Ylisastigui, L.]]
[[Category: Rochette S]]
[[Category: alpha-beta structure]]
[[Category: Roumestand C]]
[[Category: charybdotoxin-like motif]]
[[Category: Vita C]]
 
[[Category: Vizzanova J]]
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov  8 13:58:05 2007''
[[Category: Yang YS]]
[[Category: Ylisastigui L]]
Retrieved from "https://proteopedia.org/1d5q"