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PDBsum entry 3e92
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Contents |
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* Residue conservation analysis
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PDB id:
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| Name: |
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Transferase
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Title:
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Crystal structure of p38 kinase in complex with a biaryl amide inhibitor
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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, cytokine suppressive anti-inflammatory drug-binding protein, csaid-binding protein, csbp, max-interacting protein 2, map kinase mxi2, sapk2a. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. 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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0.174
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R-free:
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0.216
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Authors:
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D.O.Somers,S.Patel
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Key ref:
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I.Baldwin
et al.
(2008).
Kinase array design, back to front: biaryl amides.
Bioorg Med Chem Lett,
18,
5285-5289.
PubMed id:
DOI:
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Date:
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21-Aug-08
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Release date:
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30-Sep-08
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PROCHECK
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Headers
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References
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Q16539
(MK14_HUMAN) -
Mitogen-activated protein kinase 14 from Homo sapiens
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Seq:
Struc:
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360 a.a.
349 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 1 residue position (black
cross)
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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
18:5285-5289
(2008)
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PubMed id:
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Kinase array design, back to front: biaryl amides.
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I.Baldwin,
P.Bamborough,
C.G.Haslam,
S.S.Hunjan,
T.Longstaff,
C.J.Mooney,
S.Patel,
J.Quinn,
D.O.Somers.
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ABSTRACT
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New kinase inhibitors can be found by synthesis of targeted arrays of compounds
designed using system-based knowledge as well as through screening focused or
diverse compounds. Most array strategies aim to add functionality to a fragment
that binds in the purine subpocket of the ATP-site. Here, an alternative
pharmacophore-guided array approach is described which set out to discover novel
purine subpocket-binding groups. Results are shown for p38alpha and cFMS kinase,
for which multiple distinct series with nanomolar potency were discovered. Some
of the compounds showed potency in cell-based assays and good pharmacokinetic
properties.
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Links
