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{{STRUCTURE_1bmb|  PDB=1bmb  |  SCENE=  }}
==GRB2-SH2 DOMAIN IN COMPLEX WITH KPFY*VNVEF (PKF270-974)==
===GRB2-SH2 DOMAIN IN COMPLEX WITH KPFY*VNVEF (PKF270-974)===
<StructureSection load='1bmb' size='340' side='right' caption='[[1bmb]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
{{ABSTRACT_PUBMED_10090780}}
== Structural highlights ==
<table><tr><td colspan='2'>[[1bmb]] is a 2 chain structure with 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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BMB FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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.rcsb.org/pdb/explore.do?structureId=1bmb RCSB], [http://www.ebi.ac.uk/pdbsum/1bmb PDBsum]</span></td></tr>
<table>
== 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/bm/1bmb_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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


==About this Structure==
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>
[[1bmb]] is a 2 chain structure with 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].
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>


==See Also==
==See Also==
*[[Growth factor receptor-bound protein|Growth factor receptor-bound protein]]
*[[Growth factor receptor-bound protein|Growth factor receptor-bound protein]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:010090780</ref><references group="xtra"/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Rondeau, J M.]]
[[Category: Rondeau, J M.]]

Revision as of 18:14, 29 September 2014

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

Structural highlights

1bmb is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Gene:GRB2 (Homo sapiens)
Resources:FirstGlance, OCA, RCSB, PDBsum

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 PubMed

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.

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[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Ettmayer P, France D, Gounarides J, Jarosinski M, Martin MS, Rondeau JM, Sabio M, Topiol S, Weidmann B, Zurini M, Bair KW. Structural and conformational requirements for high-affinity binding to the SH2 domain of Grb2(1). J Med Chem. 1999 Mar 25;42(6):971-80. PMID:10090780 doi:10.1021/jm9811007

1bmb, resolution 1.80Å

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