1cj1: Difference between revisions

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[[Image:1cj1.gif|left|200px]]<br /><applet load="1cj1" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1cj1, resolution 3.0&Aring;" />
'''GROWTH FACTOR RECEPTOR BINDING PROTEIN SH2 DOMAIN (HUMAN) COMPLEXED WITH A PHOSPHOTYROSYL DERIVATIVE'''<br />


==Overview==
==GROWTH FACTOR RECEPTOR BINDING PROTEIN SH2 DOMAIN (HUMAN) COMPLEXED WITH A PHOSPHOTYROSYL DERIVATIVE==
<StructureSection load='1cj1' size='340' side='right'caption='[[1cj1]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1cj1]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CJ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CJ1 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C78:[1-[1-(6-CARBAMOYL-CYCLOHEX-2-ENYLCARBAMOYL)-CYCLOHEXYLCARBAMOYL]-2-(4-PHOSPHONOOXY-PHENYL)-+ETHYL]-CARBAMIC+ACID+3-AMINOBENZYLESTER'>C78</scene></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=1cj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cj1 OCA], [https://pdbe.org/1cj1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cj1 RCSB], [https://www.ebi.ac.uk/pdbsum/1cj1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cj1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GRB2_HUMAN GRB2_HUMAN] Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.<ref>PMID:1322798</ref> <ref>PMID:8178156</ref> <ref>PMID:19815557</ref>  Isoform 2 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Isoform 2 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death.<ref>PMID:1322798</ref> <ref>PMID:8178156</ref> <ref>PMID:19815557</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cj/1cj1_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1cj1 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Previous efforts in the search for molecules capable of blocking the associations between the activated tyrosine kinase growth factor receptors and the SH2 domain of Grb2 had resulted in the identification of 3-amino-Z-pTyr-Ac6c-Asn-NH2, a high-affinity and selective antagonist of this SH2 domain. In the present paper, we report the successful replacement of asparagine in this compound by a beta-amino acid mimetic, which brings us closer to our objective of identifying a Grb2-SH2 antagonist suitable for pharmacological investigations.
Previous efforts in the search for molecules capable of blocking the associations between the activated tyrosine kinase growth factor receptors and the SH2 domain of Grb2 had resulted in the identification of 3-amino-Z-pTyr-Ac6c-Asn-NH2, a high-affinity and selective antagonist of this SH2 domain. In the present paper, we report the successful replacement of asparagine in this compound by a beta-amino acid mimetic, which brings us closer to our objective of identifying a Grb2-SH2 antagonist suitable for pharmacological investigations.


==Disease==
Structure-based design, synthesis, and X-ray crystallography of a high-affinity antagonist of the Grb2-SH2 domain containing an asparagine mimetic.,Furet P, Garcia-Echeverria C, Gay B, Schoepfer J, Zeller M, Rahuel J J Med Chem. 1999 Jul 1;42(13):2358-63. PMID:10395476<ref>PMID:10395476</ref>
Known diseases associated with this structure: Central hypoventilation syndrome, congenital OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=100790 100790]], Haddad syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=100790 100790]]


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1CJ1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=C78:'>C78</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CJ1 OCA].
</div>
<div class="pdbe-citations 1cj1" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structure-based design, synthesis, and X-ray crystallography of a high-affinity antagonist of the Grb2-SH2 domain containing an asparagine mimetic., Furet P, Garcia-Echeverria C, Gay B, Schoepfer J, Zeller M, Rahuel J, J Med Chem. 1999 Jul 1;42(13):2358-63. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10395476 10395476]
*[[Growth factor receptor-bound proteins 3D structures|Growth factor receptor-bound proteins 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Rahuel, J.]]
[[Category: Rahuel J]]
[[Category: C78]]
[[Category: phosphotyrosine]]
[[Category: sh2 domain]]
[[Category: signal transduction]]
 
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