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PDBsum entry 2o2u
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* Residue conservation analysis
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PDB id:
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Transferase
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Title:
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Crystal structure of human jnk3 complexed with n-(3-cyano-4,5,6,7- tetrahydro-1-benzothien-2-yl)-2-fluorobenzamide
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Structure:
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Mitogen-activated protein kinase 10. Chain: a. Fragment: residues 39-402. Synonym: stress-activated protein kinase jnk3, c-jun n-terminal kinase 3, map kinase p49 3f12. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk10, jnk3, jnk3a, prkm10. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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2.45Å
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R-factor:
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0.234
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R-free:
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0.281
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Authors:
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D.Somers,P.Rowland
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Key ref:
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R.M.Angell
et al.
(2007).
N-(3-Cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amides as potent, selective, inhibitors of JNK2 and JNK3.
Bioorg Med Chem Lett,
17,
1296-1301.
PubMed id:
DOI:
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Date:
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30-Nov-06
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Release date:
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27-Feb-07
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PROCHECK
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Headers
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References
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P53779
(MK10_HUMAN) -
Mitogen-activated protein kinase 10 from Homo sapiens
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Seq:
Struc:
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464 a.a.
319 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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DOI no:
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Bioorg Med Chem Lett
17:1296-1301
(2007)
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PubMed id:
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N-(3-Cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amides as potent, selective, inhibitors of JNK2 and JNK3.
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R.M.Angell,
F.L.Atkinson,
M.J.Brown,
T.T.Chuang,
J.A.Christopher,
M.Cichy-Knight,
A.K.Dunn,
K.E.Hightower,
S.Malkakorpi,
J.R.Musgrave,
M.Neu,
P.Rowland,
R.L.Shea,
J.L.Smith,
D.O.Somers,
S.A.Thomas,
G.Thompson,
R.Wang.
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ABSTRACT
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The identification and exploration of a novel, potent and selective series of
N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amide inhibitors of JNK2 and
JNK3 kinases is described. Compounds 5a and 11a were identified as potent
inhibitors of JNK3 (pIC50 6.7 and 6.6, respectively), with essentially equal
potency against JNK2 (pIC50 6.5). Selectivity within the mitogen-activated
protein kinase (MAPK) family, against JNK1, p38alpha and ERK2, was observed for
the series. X-ray crystallography of 5e and 8a in JNK3 revealed a unique binding
mode, with the 3-cyano substituent forming an H-bond acceptor interaction with
the hinge region of the ATP-binding site.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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R.Noël,
Y.Shin,
X.Song,
Y.He,
M.Koenig,
W.Chen,
Y.Y.Ling,
L.Lin,
C.H.Ruiz,
P.LoGrasso,
M.D.Cameron,
D.R.Duckett,
and
T.M.Kamenecka
(2011).
Synthesis and SAR of 4-(pyrazol-3-yl)-pyridines as novel c-jun N-terminal kinase inhibitors.
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Bioorg Med Chem Lett,
21,
2732-2735.
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S.K.De,
E.Barile,
V.Chen,
J.L.Stebbins,
J.F.Cellitti,
T.Machleidt,
C.B.Carlson,
L.Yang,
R.Dahl,
and
M.Pellecchia
(2011).
Design, synthesis, and structure-activity relationship studies of thiophene-3-carboxamide derivatives as dual inhibitors of the c-Jun N-terminal kinase.
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Bioorg Med Chem,
19,
2582-2588.
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Y.Huang,
and
A.Dömling
(2011).
The Gewald multicomponent reaction.
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Mol Divers,
15,
3.
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T.Kamenecka,
R.Jiang,
X.Song,
D.Duckett,
W.Chen,
Y.Y.Ling,
J.Habel,
J.D.Laughlin,
J.Chambers,
M.Figuera-Losada,
M.D.Cameron,
L.Lin,
C.H.Ruiz,
and
P.V.LoGrasso
(2010).
Synthesis, biological evaluation, X-ray structure, and pharmacokinetics of aminopyrimidine c-jun-N-terminal kinase (JNK) inhibitors.
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J Med Chem,
53,
419-431.
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PDB code:
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T.Kamenecka,
J.Habel,
D.Duckett,
W.Chen,
Y.Y.Ling,
B.Frackowiak,
R.Jiang,
Y.Shin,
X.Song,
and
P.Lograsso
(2009).
Structure-Activity Relationships and X-ray Structures Describing the Selectivity of Aminopyrazole Inhibitors for c-Jun N-terminal Kinase 3 (JNK3) over p38.
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J Biol Chem,
284,
12853-12861.
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PDB codes:
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Y.Shin,
W.Chen,
J.Habel,
D.Duckett,
Y.Y.Ling,
M.Koenig,
Y.He,
T.Vojkovsky,
P.LoGrasso,
and
T.M.Kamenecka
(2009).
Synthesis and SAR of piperazine amides as novel c-jun N-terminal kinase (JNK) inhibitors.
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Bioorg Med Chem Lett,
19,
3344-3347.
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PDB code:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
