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PDBsum entry 4x7k
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Transferase/transferase inhibitor
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PDB id
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4x7k
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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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Co-crystal structure of perk bound to 4-{2-amino-3-[5-fluoro-2- (methylamino)quinazolin-6-yl]-4-methylbenzoyl}-1-methyl-2,5-diphenyl- 1,2-dihydro-3h-pyrazol-3-one inhibitor
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Structure:
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Eukaryotic translation initiation factor 2-alpha kinase 3, eukaryotic translation initiation factor 2-alpha kinase 3. Chain: a. Synonym: prkr-like endoplasmic reticulum kinase,pancreatic eif2-alpha kinase,hspek. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: eif2ak3, pek, perk. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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1.80Å
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R-factor:
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0.177
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R-free:
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0.196
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Authors:
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P.L.Shaffer,A.M.Long,H.Chen
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Key ref:
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A.L.Smith
et al.
(2015).
Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein kinase R-like endoplasmic reticulum kinase (PERK).
J Med Chem,
58,
1426-1441.
PubMed id:
DOI:
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Date:
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09-Dec-14
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Release date:
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28-Jan-15
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PROCHECK
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Headers
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References
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Q9NZJ5
(E2AK3_HUMAN) -
Eukaryotic translation initiation factor 2-alpha kinase 3 from Homo sapiens
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Seq:
Struc:
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1116 a.a.
260 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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Enzyme class:
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E.C.2.7.11.1
- non-specific serine/threonine protein kinase.
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Reaction:
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1.
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L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
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2.
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L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H+
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L-seryl-[protein]
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+
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ATP
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=
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O-phospho-L-seryl-[protein]
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+
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ADP
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+
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H(+)
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L-threonyl-[protein]
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+
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ATP
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=
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O-phospho-L-threonyl-[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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J Med Chem
58:1426-1441
(2015)
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PubMed id:
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Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein kinase R-like endoplasmic reticulum kinase (PERK).
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A.L.Smith,
K.L.Andrews,
H.Beckmann,
S.F.Bellon,
P.J.Beltran,
S.Booker,
H.Chen,
Y.A.Chung,
N.D.D'Angelo,
J.Dao,
K.R.Dellamaggiore,
P.Jaeckel,
R.Kendall,
K.Labitzke,
A.M.Long,
S.Materna-Reichelt,
P.Mitchell,
M.H.Norman,
D.Powers,
M.Rose,
P.L.Shaffer,
M.M.Wu,
J.R.Lipford.
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ABSTRACT
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The structure-based design and optimization of a novel series of selective PERK
inhibitors are described resulting in the identification of 44 as a potent,
highly selective, and orally active tool compound suitable for PERK pathway
biology exploration both in vitro and in vivo.
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Links
