1cj1: Difference between revisions
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==GROWTH FACTOR RECEPTOR BINDING PROTEIN SH2 DOMAIN (HUMAN) COMPLEXED WITH A PHOSPHOTYROSYL DERIVATIVE== | ==GROWTH FACTOR RECEPTOR BINDING PROTEIN SH2 DOMAIN (HUMAN) COMPLEXED WITH A PHOSPHOTYROSYL DERIVATIVE== | ||
<StructureSection load='1cj1' size='340' side='right' caption='[[1cj1]], [[Resolution|resolution]] 3.00Å' scene=''> | <StructureSection load='1cj1' size='340' side='right'caption='[[1cj1]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1cj1]] is a 12 chain structure. 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 [ | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <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> | </table> | ||
== Function == | == 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 == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cj/1cj1_consurf.spt"</scriptWhenChecked> | <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> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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==See Also== | ==See Also== | ||
*[[Growth factor receptor-bound | *[[Growth factor receptor-bound proteins 3D structures|Growth factor receptor-bound proteins 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Rahuel J]] | ||
Latest revision as of 14:04, 2 August 2023
GROWTH FACTOR RECEPTOR BINDING PROTEIN SH2 DOMAIN (HUMAN) COMPLEXED WITH A PHOSPHOTYROSYL DERIVATIVEGROWTH FACTOR RECEPTOR BINDING PROTEIN SH2 DOMAIN (HUMAN) COMPLEXED WITH A PHOSPHOTYROSYL DERIVATIVE
Structural highlights
FunctionGRB2_HUMAN Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.[1] [2] [3] 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.[4] [5] [6] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPrevious 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. 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[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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