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PDBsum entry 3zlx
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PDB id:
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Transferase
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Title:
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Crystal structure of mek1 in complex with fragment 18
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Structure:
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Dual specificity mitogen-activated protein kinase kinase 1. Chain: a. Synonym: map kinase kinase 1, mapkk 1, mkk1, erk activator kinase 1, mapk/erk kinase 1, mek 1, mek1. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf21
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Resolution:
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2.20Å
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R-factor:
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0.205
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R-free:
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0.236
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Authors:
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K.Amaning,M.Lowinsky,F.Vallee,V.Steier,C.Marcireau,A.Ugolini, C.Delorme,G.Mccort,C.Andouche,S.Vougier,S.Llopart,N.Halland,A.Rak
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Key ref:
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K.Amaning
et al.
(2013).
The use of virtual screening and differential scanning fluorimetry for the rapid identification of fragments active against MEK1.
Bioorg Med Chem Lett,
23,
3620-3626.
PubMed id:
DOI:
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Date:
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04-Feb-13
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Release date:
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22-May-13
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PROCHECK
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Headers
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References
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Q02750
(MP2K1_HUMAN) -
Dual specificity mitogen-activated protein kinase kinase 1 from Homo sapiens
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Seq:
Struc:
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393 a.a.
312 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.2.7.12.2
- mitogen-activated protein kinase 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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3.
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L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[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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L-tyrosyl-[protein]
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+
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ATP
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=
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O-phospho-L-tyrosyl-[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
23:3620-3626
(2013)
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PubMed id:
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The use of virtual screening and differential scanning fluorimetry for the rapid identification of fragments active against MEK1.
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K.Amaning,
M.Lowinski,
F.Vallee,
V.Steier,
C.Marcireau,
A.Ugolini,
C.Delorme,
F.Foucalt,
G.McCort,
N.Derimay,
C.Andouche,
S.Vougier,
S.Llopart,
N.Halland,
A.Rak.
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ABSTRACT
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We report the analysis of an in-house fragment screening campaign for the
oncology target MEK1. The application of virtual screening (VS) as a primary
fragment screening approach, followed by biophysical validation using
differential screening fluorimetry (DSF), with resultant binding mode
determination by X-ray crystallography (X-ray), is presented as the most time
and cost-effective combination of in silico and in vitro methods to identify
fragments. We demonstrate the effectiveness of the VS-DSF workflow for the early
identification of fragments to both 'jump-start' the drug discovery project and
to complement biochemical screening data.
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Links
