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PDBsum entry 4zxt
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PDB id:
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Transferase
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Title:
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Complex of erk2 with catechol
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Structure:
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Mitogen-activated protein kinase 1. Chain: a. Synonym: mapk 1, ert1, extracellular signal-regulated kinase 2, erk- 2, map kinase isoform p42, p42-mapk, mitogen-activated protein kinase 2, mapk 2. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk1, erk2, prkm1, prkm2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
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Resolution:
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2.00Å
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R-factor:
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0.155
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R-free:
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0.183
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Authors:
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I.Kurinov,M.Malakhova
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Key ref:
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d.o. .Y.Lim
et al.
(2016).
A natural small molecule, catechol, induces c-Myc degradation by directly targeting ERK2 in lung cancer.
Oncotarget,
7,
35001-35014.
PubMed id:
DOI:
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Date:
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20-May-15
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Release date:
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25-May-16
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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.
351 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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*
PDB and UniProt seqs differ
at 3 residue positions (black
crosses)
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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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Oncotarget
7:35001-35014
(2016)
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PubMed id:
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A natural small molecule, catechol, induces c-Myc degradation by directly targeting ERK2 in lung cancer.
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d.o. .Y.Lim,
S.H.Shin,
M.H.Lee,
M.Malakhova,
I.Kurinov,
Q.Wu,
J.Xu,
Y.Jiang,
Z.Dong,
K.Liu,
K.Y.Lee,
K.B.Bae,
B.Y.Choi,
Y.Deng,
A.Bode,
Z.Dong.
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ABSTRACT
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Various carcinogens induce EGFR/RAS/MAPK signaling, which is critical in the
development of lung cancer. In particular, constitutive activation of
extracellular signal-regulated kinase 2 (ERK2) is observed in many lung cancer
patients, and therefore developing compounds capable of targeting ERK2 in lung
carcinogenesis could be beneficial. We examined the therapeutic effect of
catechol in lung cancer treatment. Catechol suppressed anchorage-independent
growth of murine KP2 and human H460 lung cancer cell lines in a dose-dependent
manner. Catechol inhibited ERK2 kinase activity in vitro, and its direct binding
to the ERK2 active site was confirmed by X-ray crystallography. Phosphorylation
of c-Myc, a substrate of ERK2, was decreased in catechol-treated lung cancer
cells and resulted in reduced protein stability and subsequent down-regulation
of total c-Myc. Treatment with catechol induced G1 phase arrest in lung cancer
cells and decreased protein expression related to G1-S progression. In addition,
we showed that catechol inhibited the growth of both allograft and xenograft
lung cancer tumors in vivo. In summary, catechol exerted inhibitory effects on
the ERK2/c-Myc signaling axis to reduce lung cancer tumor growth in vitro and in
vivo, including a preclinical patient-derived xenograft (PDX) model. These
findings suggest that catechol, a natural small molecule, possesses potential as
a novel therapeutic agent against lung carcinogenesis in future clinical
approaches.
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Links
