1nlo: Difference between revisions
New page: left|200px<br /><applet load="1nlo" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nlo" /> '''STRUCTURE OF SIGNAL TRANSDUCTION PROTEIN, NM... |
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[[Image:1nlo.jpg|left|200px]]<br /><applet load="1nlo" size=" | [[Image:1nlo.jpg|left|200px]]<br /><applet load="1nlo" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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'''STRUCTURE OF SIGNAL TRANSDUCTION PROTEIN, NMR, MINIMIZED AVERAGE STRUCTURE'''<br /> | '''STRUCTURE OF SIGNAL TRANSDUCTION PROTEIN, NMR, MINIMIZED AVERAGE STRUCTURE'''<br /> | ||
==Overview== | ==Overview== | ||
BACKGROUND: Protein-structure-based combinatorial chemistry has recently | BACKGROUND: Protein-structure-based combinatorial chemistry has recently been used to discover several ligands containing non-peptide binding elements to the Src SH3 domain. The encoded library used has the form Cap-M1-M2-M3-PLPPLP, in which the Cap and Mi's are composed of a diverse set of organic monomers. The PLPPLP portion provided a structural bias directing the non-peptide fragment Cap-M1-M2-M3 to the SH3 specificity pocket. Fifteen ligands were selected from > 1.1 million distinct compounds. The structural basis for selection was unknown. RESULTS: The solution structures of the Src SH3 domain complexed with two ligands containing non-peptide elements selected from the library were determined by multidimensional NMR spectroscopy. The non-peptide moieties of the ligands interact with the specificity pocket of Src SH3 domain differently from peptides complexed with SH3 domains. Structural information about the ligands was used to design various homologs, whose affinities for the SH3 domain were measured. The results provide a structural basis for understanding the selection of a few optimal ligands from a large library. CONCLUSIONS: The cycle of protein-structure-based combinatorial chemistry followed by structure determination of the few highest affinity ligands provides a powerful new tool for the field of molecular recognition. | ||
==About this Structure== | ==About this Structure== | ||
1NLO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] with ACE and NH2 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http:// | 1NLO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] with <scene name='pdbligand=ACE:'>ACE</scene> and <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NLO OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
[[Category: Combs, A | [[Category: Combs, A P.]] | ||
[[Category: Feng, S.]] | [[Category: Feng, S.]] | ||
[[Category: Kapoor, T | [[Category: Kapoor, T M.]] | ||
[[Category: Schreiber, S | [[Category: Schreiber, S L.]] | ||
[[Category: Shirai, F.]] | [[Category: Shirai, F.]] | ||
[[Category: ACE]] | [[Category: ACE]] | ||
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[[Category: src]] | [[Category: src]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:07:24 2008'' | ||
Revision as of 15:07, 21 February 2008
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STRUCTURE OF SIGNAL TRANSDUCTION PROTEIN, NMR, MINIMIZED AVERAGE STRUCTURE
OverviewOverview
BACKGROUND: Protein-structure-based combinatorial chemistry has recently been used to discover several ligands containing non-peptide binding elements to the Src SH3 domain. The encoded library used has the form Cap-M1-M2-M3-PLPPLP, in which the Cap and Mi's are composed of a diverse set of organic monomers. The PLPPLP portion provided a structural bias directing the non-peptide fragment Cap-M1-M2-M3 to the SH3 specificity pocket. Fifteen ligands were selected from > 1.1 million distinct compounds. The structural basis for selection was unknown. RESULTS: The solution structures of the Src SH3 domain complexed with two ligands containing non-peptide elements selected from the library were determined by multidimensional NMR spectroscopy. The non-peptide moieties of the ligands interact with the specificity pocket of Src SH3 domain differently from peptides complexed with SH3 domains. Structural information about the ligands was used to design various homologs, whose affinities for the SH3 domain were measured. The results provide a structural basis for understanding the selection of a few optimal ligands from a large library. CONCLUSIONS: The cycle of protein-structure-based combinatorial chemistry followed by structure determination of the few highest affinity ligands provides a powerful new tool for the field of molecular recognition.
About this StructureAbout this Structure
1NLO is a Single protein structure of sequence from Gallus gallus with and as ligands. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.
ReferenceReference
Molecular basis for the binding of SH3 ligands with non-peptide elements identified by combinatorial synthesis., Feng S, Kapoor TM, Shirai F, Combs AP, Schreiber SL, Chem Biol. 1996 Aug;3(8):661-70. PMID:8807900
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