3n8m

From Proteopedia

(Difference between revisions)

Revision as of 00:00, 5 August 2016

Crystal Structure of the Grb2 SH2 Domain in Complex with An Acyclic Ligand Having the Sequence pYVNVP

Structural highlights

3n8m is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:	, ,
Related:	1bmb, 1jyr, 1tze
Gene:	GRB2, ASH (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[GRB2_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]

Publication Abstract from PubMed

The thermodynamic and structural effects of macrocyclization as a tactic for stabilizing the biologically-active conformation of Grb2 SH2 binding peptides were investigated using isothermal titration calorimetry and x-ray crystallography. 23-Membered macrocycles containing the sequence pYVN were slightly more potent than their linear controls; however, preorganization did not necessarily eventuate in a more favorable binding entropy. Structures of complexes of macrocycle 7 and its acyclic control 8 are similar except for differences in relative orientations of corresponding atoms in the linking moieties of 7 and 8. There are no differences in the number of direct or water-mediated protein-ligand contacts that might account for the less favorable binding enthalpy of 7; however, an intramolecular hydrogen bond between the pY and pY+3 residues in 8 that is absent in 7 may be a factor. These studies highlight the difficulties associated with correlating energetics and structure in protein-ligand interactions.

Thermodynamic and Structural Effects of Macrocyclization as a Constraining Method in Protein-Ligand Interactions.,Delorbe JE, Clements JH, Whiddon BB, Martin SF ACS Med Chem Lett. 2010 Nov 11;1(8):448-452. PMID:21116482^[7]

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

References

↑ Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, Ullrich A, Skolnik EY, Bar-Sagi D, Schlessinger J. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell. 1992 Aug 7;70(3):431-42. PMID:1322798
↑ Fath I, Schweighoffer F, Rey I, Multon MC, Boiziau J, Duchesne M, Tocque B. Cloning of a Grb2 isoform with apoptotic properties. Science. 1994 May 13;264(5161):971-4. PMID:8178156
↑ Pao-Chun L, Chan PM, Chan W, Manser E. Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is mediated by Grb2: an analysis of ACK1 effects on Axl signaling. J Biol Chem. 2009 Dec 11;284(50):34954-63. doi: 10.1074/jbc.M109.072660. Epub, 2009 Oct 8. PMID:19815557 doi:10.1074/jbc.M109.072660
↑ Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, Ullrich A, Skolnik EY, Bar-Sagi D, Schlessinger J. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell. 1992 Aug 7;70(3):431-42. PMID:1322798
↑ Fath I, Schweighoffer F, Rey I, Multon MC, Boiziau J, Duchesne M, Tocque B. Cloning of a Grb2 isoform with apoptotic properties. Science. 1994 May 13;264(5161):971-4. PMID:8178156
↑ Pao-Chun L, Chan PM, Chan W, Manser E. Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is mediated by Grb2: an analysis of ACK1 effects on Axl signaling. J Biol Chem. 2009 Dec 11;284(50):34954-63. doi: 10.1074/jbc.M109.072660. Epub, 2009 Oct 8. PMID:19815557 doi:10.1074/jbc.M109.072660
↑ Delorbe JE, Clements JH, Whiddon BB, Martin SF. Thermodynamic and Structural Effects of Macrocyclization as a Constraining Method in Protein-Ligand Interactions. ACS Med Chem Lett. 2010 Nov 11;1(8):448-452. PMID:21116482 doi:10.1021/ml100142y

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3n8m"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of the Grb2 SH2 Domain in Complex with An Acyclic Ligand Having the Sequence pYVNVP==
 <StructureSection load='3n8m' size='340' side='right' caption='[[3n8m]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3n8m]] 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=3N8M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N8M FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3n8m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N8M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N8M FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=6NA:HEXANOIC+ACID'>6NA</scene>, <scene name='pdbligand=9PR:N-METHYL-L-PROLINAMIDE'>9PR</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1bmb|1bmb]], [[1jyr|1jyr]], [[1tze|1tze]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRB2, ASH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRB2, ASH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3n8m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n8m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3n8m RCSB], [http://www.ebi.ac.uk/pdbsum/3n8m PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3n8m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n8m OCA], [http://pdbe.org/3n8m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3n8m RCSB], [http://www.ebi.ac.uk/pdbsum/3n8m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3n8m ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3n8m" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 26: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Clements, J H]]
 [[Category: Martin, S F]]

3n8m

From Proteopedia

Revision as of 00:00, 5 August 2016

Crystal Structure of the Grb2 SH2 Domain in Complex with An Acyclic Ligand Having the Sequence pYVNVP

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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