1zfp
From Proteopedia
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| - | [[Image:1zfp.gif|left|200px]] | + | [[Image:1zfp.gif|left|200px]] |
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| - | '''GROWTH FACTOR RECEPTOR BINDING PROTEIN SH2 DOMAIN COMPLEXED WITH A PHOSPHOTYROSYL PENTAPEPTIDE''' | + | {{Structure |
| + | |PDB= 1zfp |SIZE=350|CAPTION= <scene name='initialview01'>1zfp</scene>, resolution 1.8Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=NH2:AMINO GROUP'>NH2</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= THE PROTEIN WAS EXPRESSED AS A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''GROWTH FACTOR RECEPTOR BINDING PROTEIN SH2 DOMAIN COMPLEXED WITH A PHOSPHOTYROSYL PENTAPEPTIDE''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1ZFP is a [ | + | 1ZFP 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=1ZFP OCA]. |
==Reference== | ==Reference== | ||
| - | Structural basis for the high affinity of amino-aromatic SH2 phosphopeptide ligands., Rahuel J, Garcia-Echeverria C, Furet P, Strauss A, Caravatti G, Fretz H, Schoepfer J, Gay B, J Mol Biol. 1998 Jun 19;279(4):1013-22. PMID:[http:// | + | Structural basis for the high affinity of amino-aromatic SH2 phosphopeptide ligands., Rahuel J, Garcia-Echeverria C, Furet P, Strauss A, Caravatti G, Fretz H, Schoepfer J, Gay B, J Mol Biol. 1998 Jun 19;279(4):1013-22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9642078 9642078] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: signal transduction]] | [[Category: signal transduction]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:34:54 2008'' |
Revision as of 13:34, 20 March 2008
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| , resolution 1.8Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | THE PROTEIN WAS EXPRESSED AS A (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
GROWTH FACTOR RECEPTOR BINDING PROTEIN SH2 DOMAIN COMPLEXED WITH A PHOSPHOTYROSYL PENTAPEPTIDE
Contents |
Overview
An anthranyl moiety placed at the N terminus of a phosphotyrosine peptide potentiates the inhibitory effect of this small peptide on the binding of the Grb2 SH2 domain to the EGF receptor. Using molecular modeling procedures based on the Lck SH2 domain structure, this observation was rationalized in terms of a suitably favorable pi-pi stacking interaction between the anthranyl moiety and the arginine alphaA2 (ArgalphaA2) residue side-chain of Grb2 SH2. The crystal structure of the Grb2 SH2 domain in complex with the inhibitor 2-Abz-EpYINQ-NH2 (IC50 26 nM) has been solved in two different crystal forms at 2.1 and 1.8 A resolution. This structure confirms the modeling based on the Lck SH2 domain. The ArgalphaA2 residue is conserved in most SH2 domains. Thus, as expected, the anthranyl group also confers high affinity to small peptide ligands of other SH2 domains such as Lck-, PLC-gamma-amino-terminal and p85 amino-terminal SH2 domains as demonstrated by structure affinity relationships (SAR) data. These potent peptides with an amino-terminal surrogate group and the structure of Grb2 SH2 domain in complex with one such peptide represent good starting points for the design and optimization of new inhibitors of many SH2 domains.
Disease
Known diseases associated with this structure: Central hypoventilation syndrome, congenital OMIM:[100790], Haddad syndrome OMIM:[100790]
About this Structure
1ZFP is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for the high affinity of amino-aromatic SH2 phosphopeptide ligands., Rahuel J, Garcia-Echeverria C, Furet P, Strauss A, Caravatti G, Fretz H, Schoepfer J, Gay B, J Mol Biol. 1998 Jun 19;279(4):1013-22. PMID:9642078
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