1bmb

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[[Image:1bmb.gif|left|200px]]
 
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{{Structure
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==GRB2-SH2 DOMAIN IN COMPLEX WITH KPFY*VNVEF (PKF270-974)==
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|PDB= 1bmb |SIZE=350|CAPTION= <scene name='initialview01'>1bmb</scene>, resolution 1.80&Aring;
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<StructureSection load='1bmb' size='340' side='right'caption='[[1bmb]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>
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<table><tr><td colspan='2'>[[1bmb]] is a 2 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=1BMB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BMB FirstGlance]. <br>
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|ACTIVITY=
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
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|GENE= GRB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
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|DOMAIN=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1bmb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bmb OCA], [https://pdbe.org/1bmb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bmb RCSB], [https://www.ebi.ac.uk/pdbsum/1bmb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bmb ProSAT]</span></td></tr>
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|RELATEDENTRY=
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1bmb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bmb OCA], [http://www.ebi.ac.uk/pdbsum/1bmb PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1bmb RCSB]</span>
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== Function ==
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}}
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bm/1bmb_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1bmb ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Following earlier work on cystine-bridged peptides, cyclic phosphopeptides containing nonreducible mimics of cystine were synthesized that show high affinity and specificity toward the Src homology (SH2) domain of the growth factor receptor-binding protein (Grb2). Replacement of the cystine in the cyclic heptapeptide cyclo(CYVNVPC) by D-alpha-acetylthialysine or D-alpha-lysine gave cyclo(YVNVP(D-alpha-acetyl-thiaK)) (22) and cyclo(YVNVP(D-alpha-acetyl-K)) (30), which showed improved binding 10-fold relative to that of the control peptide KPFYVNVEF (1). NMR spectroscopy and molecular modeling experiments indicate that a beta-turn conformation centered around YVNV is essential for high-affinity binding. X-ray structure analyses show that the linear peptide 1 and the cyclic compound 21 adopt a similar binding mode with a beta-turn conformation. Our data confirm the unique structural requirements of the ligand binding site of the SH2 domain of Grb2. Moreover, the potency of our cyclic lactams can be explained by the stabilization of the beta-turn conformation by three intramolecular hydrogen bonds (one mediated by an H2O molecule). These stable and easily accessible cyclic peptides can serve as templates for the evaluation of phosphotyrosine surrogates and further chemical elaboration.
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'''GRB2-SH2 DOMAIN IN COMPLEX WITH KPFY*VNVEF (PKF270-974)'''
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Structural and conformational requirements for high-affinity binding to the SH2 domain of Grb2(1).,Ettmayer P, France D, Gounarides J, Jarosinski M, Martin MS, Rondeau JM, Sabio M, Topiol S, Weidmann B, Zurini M, Bair KW J Med Chem. 1999 Mar 25;42(6):971-80. PMID:10090780<ref>PMID:10090780</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1bmb" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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Following earlier work on cystine-bridged peptides, cyclic phosphopeptides containing nonreducible mimics of cystine were synthesized that show high affinity and specificity toward the Src homology (SH2) domain of the growth factor receptor-binding protein (Grb2). Replacement of the cystine in the cyclic heptapeptide cyclo(CYVNVPC) by D-alpha-acetylthialysine or D-alpha-lysine gave cyclo(YVNVP(D-alpha-acetyl-thiaK)) (22) and cyclo(YVNVP(D-alpha-acetyl-K)) (30), which showed improved binding 10-fold relative to that of the control peptide KPFYVNVEF (1). NMR spectroscopy and molecular modeling experiments indicate that a beta-turn conformation centered around YVNV is essential for high-affinity binding. X-ray structure analyses show that the linear peptide 1 and the cyclic compound 21 adopt a similar binding mode with a beta-turn conformation. Our data confirm the unique structural requirements of the ligand binding site of the SH2 domain of Grb2. Moreover, the potency of our cyclic lactams can be explained by the stabilization of the beta-turn conformation by three intramolecular hydrogen bonds (one mediated by an H2O molecule). These stable and easily accessible cyclic peptides can serve as templates for the evaluation of phosphotyrosine surrogates and further chemical elaboration.
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*[[Growth factor receptor-bound protein|Growth factor receptor-bound protein]]
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*[[Growth factor receptor-bound proteins 3D structures|Growth factor receptor-bound proteins 3D structures]]
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==About this Structure==
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== References ==
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1BMB is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BMB OCA].
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<references/>
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__TOC__
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==Reference==
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</StructureSection>
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Structural and conformational requirements for high-affinity binding to the SH2 domain of Grb2(1)., Ettmayer P, France D, Gounarides J, Jarosinski M, Martin MS, Rondeau JM, Sabio M, Topiol S, Weidmann B, Zurini M, Bair KW, J Med Chem. 1999 Mar 25;42(6):971-80. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10090780 10090780]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Rondeau, J M.]]
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[[Category: Rondeau JM]]
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[[Category: Zurini, M.]]
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[[Category: Zurini M]]
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[[Category: adaptor protein]]
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[[Category: ras pathway]]
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[[Category: sh2 domain]]
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[[Category: signal transduction]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:03:50 2008''
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Current revision

GRB2-SH2 DOMAIN IN COMPLEX WITH KPFY*VNVEF (PKF270-974)

PDB ID 1bmb

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