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PDBsum entry 1cj1
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Signaling protein
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PDB id
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1cj1
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Contents |
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* Residue conservation analysis
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PDB id:
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| Name: |
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Signaling protein
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Title:
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Growth factor receptor binding protein sh2 domain (human) complexed with a phosphotyrosyl derivative
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Structure:
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Protein (growth factor receptor-bound protein 2). Chain: a, b, c, d, e, f, g, h, i, j, k, l. Fragment: sh2 domain. Synonym: grb2-sh2. Engineered: yes. Other_details: complexed with phosphotyrosyl derivative
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
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Biol. unit:
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Dimer (from
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Resolution:
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3.00Å
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R-factor:
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0.305
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R-free:
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0.317
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Authors:
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J.Rahuel
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Key ref:
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P.Furet
et al.
(1999).
Structure-based design, synthesis, and X-ray crystallography of a high-affinity antagonist of the Grb2-SH2 domain containing an asparagine mimetic.
J Med Chem,
42,
2358-2363.
PubMed id:
DOI:
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Date:
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21-Apr-99
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Release date:
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22-Dec-99
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PROCHECK
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Headers
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References
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P62993
(GRB2_HUMAN) -
Growth factor receptor-bound protein 2 from Homo sapiens
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Seq:
Struc:
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217 a.a.
96 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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DOI no:
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J Med Chem
42:2358-2363
(1999)
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PubMed id:
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Structure-based design, synthesis, and X-ray crystallography of a high-affinity antagonist of the Grb2-SH2 domain containing an asparagine mimetic.
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P.Furet,
C.García-Echeverría,
B.Gay,
J.Schoepfer,
M.Zeller,
J.Rahuel.
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ABSTRACT
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Previous efforts in the search for molecules capable of blocking the
associations between the activated tyrosine kinase growth factor receptors and
the SH2 domain of Grb2 had resulted in the identification of
3-amino-Z-pTyr-Ac6c-Asn-NH2, a high-affinity and selective antagonist of this
SH2 domain. In the present paper, we report the successful replacement of
asparagine in this compound by a beta-amino acid mimetic, which brings us closer
to our objective of identifying a Grb2-SH2 antagonist suitable for
pharmacological investigations.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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K.Ogura,
T.Shiga,
M.Yokochi,
S.Yuzawa,
T.R.Burke,
and
F.Inagaki
(2008).
Solution structure of the Grb2 SH2 domain complexed with a high-affinity inhibitor.
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J Biomol NMR,
42,
197-207.
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T.R.Burke
(2006).
Development of Grb2 SH2 Domain Signaling Antagonists: A Potential New Class of Antiproliferative Agents.
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Int J Pept Res Ther,
12,
33-48.
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F.D.Lung,
C.W.Chang,
M.C.Chong,
C.C.Liou,
P.Li,
M.L.Peach,
M.C.Nicklaus,
B.S.Lou,
and
P.P.Roller
(2005).
Small nonphosphorylated Grb2-SH2 domain antagonists evaluated by surface plasmon resonance technology.
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Biopolymers,
80,
628-635.
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F.D.Lung,
and
J.Y.Tsai
(2003).
Grb2 SH2 domain-binding peptide analogs as potential anticancer agents.
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Biopolymers,
71,
132-140.
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A.V.Veselovsky,
Y.D.Ivanov,
A.S.Ivanov,
A.I.Archakov,
P.Lewi,
and
P.Janssen
(2002).
Protein-protein interactions: mechanisms and modification by drugs.
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J Mol Recognit,
15,
405-422.
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G.Scapin
(2002).
Structural biology in drug design: selective protein kinase inhibitors.
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Drug Discov Today,
7,
601-611.
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S.C.Pero,
L.Oligino,
R.J.Daly,
A.L.Soden,
C.Liu,
P.P.Roller,
P.Li,
and
D.N.Krag
(2002).
Identification of novel non-phosphorylated ligands, which bind selectively to the SH2 domain of Grb7.
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J Biol Chem,
277,
11918-11926.
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M.Vidal,
V.Gigoux,
and
C.Garbay
(2001).
SH2 and SH3 domains as targets for anti-proliferative agents.
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Crit Rev Oncol Hematol,
40,
175-186.
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A.M.Petros,
D.G.Nettesheim,
Y.Wang,
E.T.Olejniczak,
R.P.Meadows,
J.Mack,
K.Swift,
E.D.Matayoshi,
H.Zhang,
C.B.Thompson,
and
S.W.Fesik
(2000).
Rationale for Bcl-xL/Bad peptide complex formation from structure, mutagenesis, and biophysical studies.
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Protein Sci,
9,
2528-2534.
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PDB code:
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P.Furet,
G.Caravatti,
A.A.Denholm,
A.Faessler,
H.Fretz,
C.García-Echeverría,
B.Gay,
E.Irving,
N.J.Press,
J.Rahuel,
J.Schoepfer,
and
C.V.Walker
(2000).
Structure-based design and synthesis of phosphinate isosteres of phosphotyrosine for incorporation in Grb2-SH2 domain inhibitors. Part 1.
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Bioorg Med Chem Lett,
10,
2337-2341.
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P.J.Gane,
and
P.M.Dean
(2000).
Recent advances in structure-based rational drug design.
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Curr Opin Struct Biol,
10,
401-404.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
