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PDBsum entry 3i5z
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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 bound to (s)-n-(2-hydroxy-1-phenylethyl)-4- (5-methyl-2-(phenylamino)pyrimidin-4-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: erk2, mapk1, prkm1, prkm2. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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2.20Å
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R-factor:
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0.217
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R-free:
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0.258
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Authors:
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M.D.Jacobs,X.Xie
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Key ref:
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A.M.Aronov
et al.
(2009).
Structure-guided design of potent and selective pyrimidylpyrrole inhibitors of extracellular signal-regulated kinase (ERK) using conformational control.
J Med Chem,
52,
6362-6368.
PubMed id:
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Date:
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06-Jul-09
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Release date:
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12-Jan-10
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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.
331 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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J Med Chem
52:6362-6368
(2009)
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PubMed id:
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Structure-guided design of potent and selective pyrimidylpyrrole inhibitors of extracellular signal-regulated kinase (ERK) using conformational control.
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A.M.Aronov,
Q.Tang,
G.Martinez-Botella,
G.W.Bemis,
J.Cao,
G.Chen,
N.P.Ewing,
P.J.Ford,
U.A.Germann,
J.Green,
M.R.Hale,
M.Jacobs,
J.W.Janetka,
F.Maltais,
W.Markland,
M.N.Namchuk,
S.Nanthakumar,
S.Poondru,
J.Straub,
E.ter Haar,
X.Xie.
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ABSTRACT
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The Ras/Raf/MEK/ERK signal transduction, an oncogenic pathway implicated in a
variety of human cancers, is a key target in anticancer drug design. A novel
series of pyrimidylpyrrole ERK inhibitors has been identified. Discovery of a
conformational change for lead compound 2, when bound to ERK2 relative to
antitarget GSK3, enabled structure-guided selectivity optimization, which led to
the discovery of 11e, a potent, selective, and orally bioavailable 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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S.Y.Lu,
Y.J.Jiang,
J.Lv,
J.W.Zou,
and
T.X.Wu
(2011).
Role of bridging water molecules in GSK3β-inhibitor complexes: insights from QM/MM, MD, and molecular docking studies.
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J Comput Chem,
32,
1907-1918.
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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.
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Links
