From Proteopedia
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| - | [[Image:1shd.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1shd.png|left|200px]] |
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| | {{STRUCTURE_1shd| PDB=1shd | SCENE= }} | | {{STRUCTURE_1shd| PDB=1shd | SCENE= }} |
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| - | '''PEPTIDE INHIBITORS OF SRC SH3-SH2-PHOSPHOPROTEIN INTERACTIONS'''
| + | ===PEPTIDE INHIBITORS OF SRC SH3-SH2-PHOSPHOPROTEIN INTERACTIONS=== |
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| - | ==Overview==
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| - | Activated pp60c-src has been implicated in a number of human malignancies including colon carcinoma and breast adenocarcinoma. Association of the src SH2 domain with tyrosine-phosphorylated proteins plays a role in src-mediated signal transduction. Inhibitors of src SH2 domain-phosphoprotein interactions are, thus, of great interest in defining the role(s) of src in signal transduction pathways. To facilitate such studies, an enzyme-linked immunosorbent assay (ELISA) was developed to detect inhibitors of src SH2-phosphoprotein interactions. This assay measures inhibition of binding of a fusion construct (glutathione S-transferase src SH3-SH2) with autophosphorylated epidermal growth factor receptor tyrosine kinase domain. Activities of phosphopeptide segments derived from potential src SH2 cognate phosphoprotein partners were determined, with the focal adhesion kinase-derived segment VSETDDY*AEIIDE yielding the highest inhibitory activity. Structure activity studies starting from acetyl (Ac)-Y*EEIE have identified Ac-Y*Y*Y*IE as the most active compound screened in the ELISA. This compound is at least 20-fold more active than the parent peptide Ac-Y*EEIE. A high resolution (2 A) crystal structure of human src SH2 complexed with Ac-Y*EEIE was obtained and provided a useful framework for understanding the structure-activity relationships. Additionally, Ac-Y*EEIE was able to block interactions between src and its cellular phosphoprotein partners in vanadate-treated cell lysates from MDA-MB-468 breast carcinoma cells. However, it is unable to abrogate proliferation of MDA-MB-468 cells in culture, presumably because of poor cell penetration and/or lability of the phosphate group on tyrosine.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_7527393}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 7527393 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_7527393}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Gilmer, T.]] | | [[Category: Gilmer, T.]] |
| | [[Category: Jordan, S.]] | | [[Category: Jordan, S.]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 08:42:28 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 19:11:39 2008'' |
Revision as of 16:11, 27 July 2008
Template:STRUCTURE 1shd
PEPTIDE INHIBITORS OF SRC SH3-SH2-PHOSPHOPROTEIN INTERACTIONS
Template:ABSTRACT PUBMED 7527393
About this Structure
1SHD is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Peptide inhibitors of src SH3-SH2-phosphoprotein interactions., Gilmer T, Rodriguez M, Jordan S, Crosby R, Alligood K, Green M, Kimery M, Wagner C, Kinder D, Charifson P, et al., J Biol Chem. 1994 Dec 16;269(50):31711-9. PMID:7527393
Page seeded by OCA on Sun Jul 27 19:11:39 2008
