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PDBsum entry 4h1m
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Transferase/transferase inhibitor
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PDB id
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4h1m
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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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Crystal structure of pyk2 with the indole 10c
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Structure:
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Protein-tyrosine kinase 2-beta. Chain: a. Fragment: protein kinase domain (unp residues 416-692). Synonym: pyk2, calcium-dependent tyrosine kinase, cadtk, calcium- regulated non-receptor proline-rich tyrosine kinase, cell adhesion kinase beta, cak-beta, cakb, focal adhesion kinase 2, fadk 2, proline-rich tyrosine kinase 2, related adhesion focal tyrosine kinase, raftk. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: ptk2b, fak2, pyk2, raftk. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108
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Resolution:
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1.99Å
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R-factor:
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0.226
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R-free:
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0.296
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Authors:
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S.Han
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Key ref:
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S.K.Bhattacharya
et al.
(2012).
Identification of novel series of pyrazole and indole-urea based DFG-out PYK2 inhibitors.
Bioorg Med Chem Lett,
22,
7523-7529.
PubMed id:
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Date:
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10-Sep-12
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Release date:
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28-Nov-12
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PROCHECK
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Headers
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References
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Q14289
(FAK2_HUMAN) -
Protein-tyrosine kinase 2-beta from Homo sapiens
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Seq:
Struc:
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1009 a.a.
256 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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Bioorg Med Chem Lett
22:7523-7529
(2012)
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PubMed id:
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Identification of novel series of pyrazole and indole-urea based DFG-out PYK2 inhibitors.
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S.K.Bhattacharya,
G.E.Aspnes,
S.W.Bagley,
M.Boehm,
A.D.Brosius,
L.Buckbinder,
J.S.Chang,
J.Dibrino,
H.Eng,
K.S.Frederick,
D.A.Griffith,
M.C.Griffor,
C.R.Guimarães,
A.Guzman-Perez,
S.Han,
A.S.Kalgutkar,
J.Klug-McLeod,
C.Garcia-Irizarry,
J.Li,
B.Lippa,
D.A.Price,
J.A.Southers,
D.P.Walker,
L.Wei,
J.Xiao,
M.P.Zawistoski,
X.Zhao.
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ABSTRACT
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Previous drug discovery efforts identified classical PYK2 kinase inhibitors such
as 2 and 3 that possess selectivity for PYK2 over its intra-family isoform FAK.
Efforts to identify more kinome-selective chemical matter that stabilize a
DFG-out conformation of the enzyme are described herein. Two sub-series of PYK2
inhibitors, an indole carboxamide-urea and a pyrazole-urea have been identified
and found to have different binding interactions with the hinge region of PYK2.
These leads proved to be more selective than the original classical inhibitors.
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