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PDBsum entry 6s3c
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Peptide binding protein
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PDB id
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6s3c
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PDB id:
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| Name: |
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Peptide binding protein
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Title:
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Fragment az-019 binding at the p53pt387/14-3-3 sigma interface
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Structure:
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14-3-3 protein sigma. Chain: a. Synonym: epithelial cell marker protein 1,stratifin. Engineered: yes. P53pt387. Chain: p. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: sfn, hme1. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606
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Resolution:
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2.00Å
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R-factor:
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0.231
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R-free:
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0.252
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Authors:
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S.Genet,M.Wolter,X.Guillory,B.Somsen,S.Leysen,P.Castaldi,C.Ottmann
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Key ref:
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X.Guillory
et al.
(2020).
Fragment-based Differential Targeting of PPI Stabilizer Interfaces.
J Med Chem,
63,
6694-6707.
PubMed id:
DOI:
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Date:
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25-Jun-19
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Release date:
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17-Jun-20
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PROCHECK
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Headers
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References
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P31947
(1433S_HUMAN) -
14-3-3 protein sigma from Homo sapiens
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Seq:
Struc:
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248 a.a.
229 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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DOI no:
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J Med Chem
63:6694-6707
(2020)
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PubMed id:
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Fragment-based Differential Targeting of PPI Stabilizer Interfaces.
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X.Guillory,
M.Wolter,
S.Leysen,
J.F.Neves,
A.Kuusk,
S.Genet,
B.Somsen,
J.K.Morrow,
E.Rivers,
L.van Beek,
J.Patel,
R.Goodnow,
H.Schoenherr,
N.Fuller,
Q.Cao,
R.G.Doveston,
L.Brunsveld,
M.R.Arkin,
P.Castaldi,
H.Boyd,
I.Landrieu,
H.Chen,
C.Ottmann.
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ABSTRACT
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Stabilization of protein-protein interactions (PPIs) holds great potential for
therapeutic agents, as illustrated by the successful drugs rapamycin and
lenalidomide. However, how such interface-binding molecules can be created in a
rational, bottom-up manner is a largely unanswered question. We report here how
a fragment-based approach can be used to identify chemical starting points for
the development of small-molecule stabilizers that differentiate between two
different PPI interfaces of the adapter protein 14-3-3. The fragments
discriminately bind to the interface of 14-3-3 with the recognition motif of
either the tumor suppressor protein p53 or the oncogenic transcription factor
TAZ. This X-ray crystallography driven study shows that the rim of the interface
of individual 14-3-3 complexes can be targeted in a differential manner with
fragments that represent promising starting points for the development of
specific 14-3-3 PPI stabilizers.
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Links
