1bmb
From Proteopedia
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| - | [[Image:1bmb.gif|left|200px]] | + | [[Image:1bmb.gif|left|200px]] |
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| - | '''GRB2-SH2 DOMAIN IN COMPLEX WITH KPFY*VNVEF (PKF270-974)''' | + | {{Structure |
| + | |PDB= 1bmb |SIZE=350|CAPTION= <scene name='initialview01'>1bmb</scene>, resolution 1.80Å | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= | ||
| + | |GENE= GRB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''GRB2-SH2 DOMAIN IN COMPLEX WITH KPFY*VNVEF (PKF270-974)''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1BMB is a [ | + | 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]. |
==Reference== | ==Reference== | ||
| - | 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:// | + | 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] |
[[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 10:12:54 2008'' |
Revision as of 08:12, 20 March 2008
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| , resolution 1.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | GRB2 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
GRB2-SH2 DOMAIN IN COMPLEX WITH KPFY*VNVEF (PKF270-974)
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Central hypoventilation syndrome, congenital OMIM:[100790], Haddad syndrome OMIM:[100790]
About this Structure
1BMB is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
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