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PDBsum entry 2gtn
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Contents |
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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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Mutated map kinase p38 (mus musculus) in complex with inhbitor pg- 951717
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Structure:
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Mitogen-activated protein kinase 14. Chain: a. Synonym: mitogen-activated protein kinase p38 alpha, map kinase p38 alpha, crk1. Engineered: yes
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Source:
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Mus musculus. House mouse. Organism_taxid: 10090. Gene: mapk14. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
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Resolution:
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1.80Å
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R-factor:
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0.203
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R-free:
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0.248
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Authors:
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R.L.Walter,M.J.Mekel,A.G.Evdokimov,M.E.Pokross,M.Sabat
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Key ref:
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M.Sabat
et al.
(2006).
The development of novel C-2, C-8, and N-9 trisubstituted purines as inhibitors of TNF-alpha production.
Bioorg Med Chem Lett,
16,
4360-4365.
PubMed id:
DOI:
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Date:
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28-Apr-06
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Release date:
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11-Jul-06
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PROCHECK
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Headers
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References
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P47811
(MK14_MOUSE) -
Mitogen-activated protein kinase 14 from Mus musculus
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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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Bioorg Med Chem Lett
16:4360-4365
(2006)
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PubMed id:
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The development of novel C-2, C-8, and N-9 trisubstituted purines as inhibitors of TNF-alpha production.
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M.Sabat,
J.C.Vanrens,
M.P.Clark,
T.A.Brugel,
J.Maier,
R.G.Bookland,
M.J.Laufersweiler,
S.K.Laughlin,
A.Golebiowski,
B.De,
L.C.Hsieh,
R.L.Walter,
M.J.Mekel,
M.J.Janusz.
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ABSTRACT
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A series of C-2, C-8, and N-9 trisubstituted purine based inhibitors of
TNF-alpha production are described. The most potent analogs showed low nanomolar
activity against LPS-induced TNF-alpha production in a THP-1 cell based assay.
The SAR of the series was optimized with the aid of X-ray co-crystal structures
of these inhibitors bound with mutated p38 (mp38).
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Links
