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PDBsum entry 3s3i
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Transferase/transferase inhibitor
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PDB id
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3s3i
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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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P38 kinase crystal structure in complex with small molecule inhibitor
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Structure:
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Mitogen-activated protein kinase 14. Chain: a. Synonym: map kinase 14, mapk 14, cytokine suppressive anti- inflammatory drug-binding protein, csaid-binding protein, csbp, map kinase mxi2, max-interacting protein 2, mitogen-activated protein kinase p38 alpha, map kinase p38 alpha, sapk2a. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: csbp, csbp1, csbp2, cspb1, mapk14, mxi2. 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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0.233
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R-free:
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0.258
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Authors:
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V.Segarra,J.Aiguade,R.Roca,M.Fisher,M.Lamers
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Key ref:
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J.Aiguadé
et al.
(2012).
Novel triazolopyridylbenzamides as potent and selective p38α inhibitors.
Bioorg Med Chem Lett,
22,
3431-3436.
PubMed id:
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Date:
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18-May-11
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Release date:
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04-Apr-12
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PROCHECK
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Headers
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References
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Q16539
(MK14_HUMAN) -
Mitogen-activated protein kinase 14 from Homo sapiens
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Seq:
Struc:
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360 a.a.
349 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.2.7.11.24
- mitogen-activated 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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Bioorg Med Chem Lett
22:3431-3436
(2012)
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PubMed id:
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Novel triazolopyridylbenzamides as potent and selective p38α inhibitors.
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J.Aiguadé,
C.Balagué,
I.Carranco,
F.Caturla,
M.Domínguez,
P.Eastwood,
C.Esteve,
J.González,
W.Lumeras,
A.Orellana,
S.Preciado,
R.Roca,
L.Vidal,
B.Vidal.
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ABSTRACT
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A new class of p38α inhibitors based on a biaryl-triazolopyridine scaffold was
investigated. X-ray crystallographic data of the initial lead compound
cocrystallised with p38α was crucial in order to uncover a unique binding mode
of the inhibitor to the hinge region via a pair of water molecules. Synthesis
and SAR was directed towards the improvement of binding affinity, as well as
ADME properties for this new class of p38α inhibitors and ultimately afforded
compounds showing good in vivo efficacy.
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