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PDBsum entry 2ojg
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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 erk2 in complex with n,n-dimethyl-4-(4-phenyl-1h- pyrazol-3-yl)-1h-pyrrole-2-carboxamide
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Structure:
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Mitogen-activated protein kinase 1. Chain: a. Synonym: extracellular signal-regulated kinase 2, erk-2, mitogen- activated protein kinase 2, map kinase 2, mapk 2, p42-mapk, ert1. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk1, erk2, prkm1. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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2.00Å
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R-factor:
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0.220
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R-free:
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0.260
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Authors:
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X.Xie,M.D.Jacobs
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Key ref:
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A.M.Aronov
et al.
(2007).
Flipped out: structure-guided design of selective pyrazolylpyrrole ERK inhibitors.
J Med Chem,
50,
1280-1287.
PubMed id:
DOI:
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Date:
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12-Jan-07
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Release date:
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06-Feb-07
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PROCHECK
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Headers
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References
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P28482
(MK01_HUMAN) -
Mitogen-activated protein kinase 1 from Homo sapiens
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Seq:
Struc:
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360 a.a.
337 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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J Med Chem
50:1280-1287
(2007)
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PubMed id:
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Flipped out: structure-guided design of selective pyrazolylpyrrole ERK inhibitors.
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A.M.Aronov,
C.Baker,
G.W.Bemis,
J.Cao,
G.Chen,
P.J.Ford,
U.A.Germann,
J.Green,
M.R.Hale,
M.Jacobs,
J.W.Janetka,
F.Maltais,
G.Martinez-Botella,
M.N.Namchuk,
J.Straub,
Q.Tang,
X.Xie.
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ABSTRACT
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The Ras/Raf/MEK/ERK signal transduction is a key oncogenic pathway implicated in
a variety of human cancers. We have identified a novel series of
pyrazolylpyrroles as inhibitors of ERK. Aided by the discovery of two distinct
binding modes for the pyrazolylpyrrole scaffold, structure-guided optimization
culminated in the discovery of 6p, a potent and selective inhibitor of ERK.
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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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J.L.Yap,
S.Worlikar,
A.D.MacKerell,
P.Shapiro,
and
S.Fletcher
(2011).
Small-molecule inhibitors of the ERK signaling pathway: Towards novel anticancer therapeutics.
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ChemMedChem,
6,
38-48.
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R.Y.Huang,
M.Y.Li,
M.K.Hsin,
M.J.Underwood,
L.T.Ma,
T.S.Mok,
T.D.Warner,
and
G.G.Chen
(2011).
4-Methylnitrosamino-1-3-pyridyl-1-butanone (NNK) promotes lung cancer cell survival by stimulating thromboxane A2 and its receptor.
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Oncogene,
30,
106-116.
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S.Ramaswamy,
I.Yen,
S.Sideris,
S.Malek,
and
C.E.Heise
(2010).
A plate-based assay to measure cellular ERK substrate phosphorylation: utility for drug discovery of the MAPK-signaling cascade.
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Assay Drug Dev Technol,
8,
497-503.
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T.Shen,
J.Lee,
E.Lee,
S.H.Kim,
T.W.Kim,
and
J.Y.Cho
(2010).
Cafestol, a coffee-specific diterpene, is a novel extracellular signal-regulated kinase inhibitor with AP-1-targeted inhibition of prostaglandin E2 production in lipopolysaccharide-activated macrophages.
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Biol Pharm Bull,
33,
128-132.
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K.Burkhard,
S.Smith,
R.Deshmukh,
A.D.MacKerell,
and
P.Shapiro
(2009).
Development of extracellular signal-regulated kinase inhibitors.
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Curr Top Med Chem,
9,
678-689.
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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.Kim,
K.Kim,
H.Lee,
S.Han,
Y.S.Lee,
J.Choe,
Y.M.Kim,
J.H.Hahn,
J.Y.Ro,
and
D.Jeoung
(2009).
Celastrol binds to ERK and inhibits FcepsilonRI signaling to exert an anti-allergic effect.
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Eur J Pharmacol,
612,
131-142.
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F.Chen,
A.D.Mackerell,
Y.Luo,
and
P.Shapiro
(2008).
Using Caenorhabditis elegans as a model organism for evaluating extracellular signal-regulated kinase docking domain inhibitors.
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J Cell Commun Signal,
2,
81-92.
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Y.Z.Xiong,
and
P.Y.Chen
(2008).
ONIOM DFT/PM3 calculation on the interaction between STI-571 and abelson tyrosine kinase.
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J Mol Model,
14,
1083-1086.
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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
codes are
shown on the right.
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Links
