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PDBsum entry 1nlp
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Complex (transferase/peptide)
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PDB id
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1nlp
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Molecular basis for the binding of sh3 ligands with non-Peptide elements identified by combinatorial synthesis.
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Authors
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S.Feng,
T.M.Kapoor,
F.Shirai,
A.P.Combs,
S.L.Schreiber.
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Ref.
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Chem Biol, 1996,
3,
661-670.
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
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Abstract
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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.
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Secondary reference #1
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Title
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Protein structure-Based combinatorial chemistry: discovery of non- Peptide binding elements to src sh3 domain
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Authors
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A.P.Combs,
T.M.Kapoor,
S.Feng,
J.K.Chen,
L.F.Daude-Snow,
S.L.Schreiber.
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Ref.
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j am chem soc, 1996,
118,
287.
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Secondary reference #2
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Title
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Specific interactions outside the proline-Rich core of two classes of src homology 3 ligands.
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Authors
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S.Feng,
C.Kasahara,
R.J.Rickles,
S.L.Schreiber.
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Ref.
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Proc Natl Acad Sci U S A, 1995,
92,
12408-12415.
[DOI no: ]
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PubMed id
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Secondary reference #3
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Title
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Structural basis for the binding of proline-Rich peptides to sh3 domains.
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Authors
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H.Yu,
J.K.Chen,
S.Feng,
D.C.Dalgarno,
A.W.Brauer,
S.L.Schreiber.
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Ref.
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Cell, 1994,
76,
933-945.
[DOI no: ]
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PubMed id
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Secondary reference #4
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Title
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Two binding orientations for peptides to the src sh3 domain: development of a general model for sh3-Ligand interactions.
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Authors
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S.Feng,
J.K.Chen,
H.Yu,
J.A.Simon,
S.L.Schreiber.
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Ref.
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Science, 1994,
266,
1241-1247.
[DOI no: ]
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PubMed id
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Secondary reference #5
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Title
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Solution structure of the sh3 domain of src and identification of its ligand-Binding site.
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Authors
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H.Yu,
M.K.Rosen,
T.B.Shin,
C.Seidel-Dugan,
J.S.Brugge,
S.L.Schreiber.
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Ref.
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Science, 1992,
258,
1665-1668.
[DOI no: ]
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PubMed id
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