1kcn

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(New page: 200px<br /><applet load="1kcn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kcn" /> '''Structure of e109 Zeta Peptide, an Antagonis...)
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'''Structure of e109 Zeta Peptide, an Antagonist of the High-Affinity IgE Receptor'''<br />
'''Structure of e109 Zeta Peptide, an Antagonist of the High-Affinity IgE Receptor'''<br />
==Overview==
==Overview==
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Recently we described a family of peptides, unrelated in sequence to IgE, that form stable beta-hairpins in solution and inhibit IgE activity in the, microM range [Nakamura, G. R., Starovasnik, M. A., Reynolds, M. E. &amp;, Lowman, H. B. (2001) Biochemistry 40, 9828-9835]. Using an expanded set of, peptide-phage libraries, we found a simpler motif, X(2)CPX(2)CYX, for, binding to the high-affinity IgE receptor. In solution, one of these, peptides spontaneously formed a covalent antiparallel dimer. We, subsequently linked these monomers in a single-chain construct on phage, and optimized receptor binding. Ultimately, peptides with 30 nM affinity, were produced. NMR studies showed that the peptide adopts a stable fold, consisting of two "zeta" (zeta)-shaped moieties. Structure-activity, analyses reveal a single binding site created by the zeta-dimer, with two, tyrosine residues important for structural stability and two proline, residues important for Fc epsilon RI binding. The peptides inhibit, histamine release from cultured cells and are extremely stable in, biological fluids. The zeta peptides appear to act as competitive IgE, inhibitors and suggest possibilities for design of novel IgE antagonists.
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Recently we described a family of peptides, unrelated in sequence to IgE, that form stable beta-hairpins in solution and inhibit IgE activity in the microM range [Nakamura, G. R., Starovasnik, M. A., Reynolds, M. E. &amp; Lowman, H. B. (2001) Biochemistry 40, 9828-9835]. Using an expanded set of peptide-phage libraries, we found a simpler motif, X(2)CPX(2)CYX, for binding to the high-affinity IgE receptor. In solution, one of these peptides spontaneously formed a covalent antiparallel dimer. We subsequently linked these monomers in a single-chain construct on phage and optimized receptor binding. Ultimately, peptides with 30 nM affinity were produced. NMR studies showed that the peptide adopts a stable fold consisting of two "zeta" (zeta)-shaped moieties. Structure-activity analyses reveal a single binding site created by the zeta-dimer, with two tyrosine residues important for structural stability and two proline residues important for Fc epsilon RI binding. The peptides inhibit histamine release from cultured cells and are extremely stable in biological fluids. The zeta peptides appear to act as competitive IgE inhibitors and suggest possibilities for design of novel IgE antagonists.
==About this Structure==
==About this Structure==
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1KCN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1KCN OCA].
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1KCN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KCN OCA].
==Reference==
==Reference==
Stable "zeta" peptides that act as potent antagonists of the high-affinity IgE receptor., Nakamura GR, Reynolds ME, Chen YM, Starovasnik MA, Lowman HB, Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1303-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11830661 11830661]
Stable "zeta" peptides that act as potent antagonists of the high-affinity IgE receptor., Nakamura GR, Reynolds ME, Chen YM, Starovasnik MA, Lowman HB, Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1303-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11830661 11830661]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: Chen, Y.M.]]
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[[Category: Chen, Y M.]]
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[[Category: Lowman, H.B.]]
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[[Category: Lowman, H B.]]
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[[Category: Nakamura, G.R.]]
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[[Category: Nakamura, G R.]]
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[[Category: Reynolds, M.E.]]
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[[Category: Reynolds, M E.]]
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[[Category: Starovasnik, M.A.]]
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[[Category: Starovasnik, M A.]]
[[Category: NH2]]
[[Category: NH2]]
[[Category: "zeta" structure]]
[[Category: "zeta" structure]]
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[[Category: helical]]
[[Category: helical]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 01:07:40 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:32:35 2008''

Revision as of 11:32, 21 February 2008


1kcn

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Structure of e109 Zeta Peptide, an Antagonist of the High-Affinity IgE Receptor

Overview

Recently we described a family of peptides, unrelated in sequence to IgE, that form stable beta-hairpins in solution and inhibit IgE activity in the microM range [Nakamura, G. R., Starovasnik, M. A., Reynolds, M. E. & Lowman, H. B. (2001) Biochemistry 40, 9828-9835]. Using an expanded set of peptide-phage libraries, we found a simpler motif, X(2)CPX(2)CYX, for binding to the high-affinity IgE receptor. In solution, one of these peptides spontaneously formed a covalent antiparallel dimer. We subsequently linked these monomers in a single-chain construct on phage and optimized receptor binding. Ultimately, peptides with 30 nM affinity were produced. NMR studies showed that the peptide adopts a stable fold consisting of two "zeta" (zeta)-shaped moieties. Structure-activity analyses reveal a single binding site created by the zeta-dimer, with two tyrosine residues important for structural stability and two proline residues important for Fc epsilon RI binding. The peptides inhibit histamine release from cultured cells and are extremely stable in biological fluids. The zeta peptides appear to act as competitive IgE inhibitors and suggest possibilities for design of novel IgE antagonists.

About this Structure

1KCN is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.

Reference

Stable "zeta" peptides that act as potent antagonists of the high-affinity IgE receptor., Nakamura GR, Reynolds ME, Chen YM, Starovasnik MA, Lowman HB, Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1303-8. PMID:11830661

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