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PDBsum entry 4kab
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Transferase/transferase inhibitor
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PDB id
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4kab
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PDB id:
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| Name: |
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Transferase/transferase inhibitor
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Title:
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Focal adhesion kinase catalytic domain in complex with 3-methyl-1,4- dihydro-pyrazolo[4,5-c]pyrazole
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Structure:
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Focal adhesion kinase 1. Chain: a, b. Fragment: kinase domain, unp residues 410-686. Synonym: fadk 1, focal adhesion kinase-related nonkinase, frnk, protein phosphatase 1 regulatory subunit 71, ppp1r71, protein- tyrosine kinase 2, p125fak, pp125fak. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: ptk2, fak, fak1. Expressed in: trichoplusia ni. Expression_system_taxid: 7111
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Resolution:
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2.71Å
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R-factor:
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0.173
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R-free:
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0.219
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Authors:
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D.Musil,U.Graedler,T.Heinrich,M.Lehmann,V.Dresing
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Key ref:
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U.Grädler
et al.
(2013).
Fragment-based discovery of focal adhesion kinase inhibitors.
Bioorg Med Chem Lett,
23,
5401-5409.
PubMed id:
DOI:
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Date:
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22-Apr-13
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Release date:
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11-Sep-13
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PROCHECK
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Headers
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References
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Q05397
(FAK1_HUMAN) -
Focal adhesion kinase 1 from Homo sapiens
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Seq:
Struc:
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1052 a.a.
255 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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Enzyme class:
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E.C.2.7.10.2
- non-specific protein-tyrosine kinase.
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Reaction:
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L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
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L-tyrosyl-[protein]
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+
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ATP
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=
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O-phospho-L-tyrosyl-[protein]
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+
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ADP
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Bioorg Med Chem Lett
23:5401-5409
(2013)
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PubMed id:
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Fragment-based discovery of focal adhesion kinase inhibitors.
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U.Grädler,
J.Bomke,
D.Musil,
V.Dresing,
M.Lehmann,
G.Hölzemann,
H.Greiner,
C.Esdar,
M.Krier,
T.Heinrich.
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ABSTRACT
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Chemically diverse fragment hits of focal adhesion kinase (FAK) were discovered
by surface plasmon resonance (SPR) screening of our in-house fragment library.
Site specific binding of the primary hits was confirmed in a competition setup
using a high-affinity ATP-site inhibitor of FAK. Protein crystallography
revealed the binding mode of 41 out of 48 selected fragment hits within the
ATP-site. Structural comparison of the fragment binding modes with a DFG-out
inhibitor of FAK initiated first synthetic follow-up optimization leading to
improved binding affinity.
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Links
