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PDBsum entry 2vwz
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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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Ephb4 kinase domain inhibitor complex
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Structure:
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Ephrin type-b receptor 4. Chain: a. Fragment: protein kinase domain, residues 598-899. Synonym: ephb4 receptor tyrosine kinase, tyrosine-protein kinase receptor htk, tyrosine-protein kinase tyro11. 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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1.65Å
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R-factor:
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0.170
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R-free:
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0.205
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Authors:
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J.Read,C.A.Brassington,I.Green,E.J.Mccall,A.L.Valentine,D.Barratt, A.G.Leach,J.G.Kettle
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Key ref:
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C.Bardelle
et al.
(2008).
Inhibitors of the tyrosine kinase EphB4. Part 2: structure-based discovery and optimisation of 3,5-bis substituted anilinopyrimidines.
Bioorg Med Chem Lett,
18,
5717-5721.
PubMed id:
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Date:
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30-Jun-08
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Release date:
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28-Oct-08
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PROCHECK
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Headers
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References
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P54760
(EPHB4_HUMAN) -
Ephrin type-B receptor 4 from Homo sapiens
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Seq:
Struc:
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987 a.a.
274 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.2.7.10.1
- receptor protein-tyrosine kinase.
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Reaction:
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L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + 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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Bioorg Med Chem Lett
18:5717-5721
(2008)
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PubMed id:
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Inhibitors of the tyrosine kinase EphB4. Part 2: structure-based discovery and optimisation of 3,5-bis substituted anilinopyrimidines.
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C.Bardelle,
T.Coleman,
D.Cross,
S.Davenport,
J.G.Kettle,
E.J.Ko,
A.G.Leach,
A.Mortlock,
J.Read,
N.J.Roberts,
P.Robins,
E.J.Williams.
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ABSTRACT
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Crystallographic studies of a range of 3-substituted anilinopyrimidine
inhibitors of EphB4 have highlighted two alternative C-2 aniline conformations
and this discovery has been exploited in the design of a highly potent series of
3,5-disubstituted anilinopyrimidines. The observed range of cellular activities
has been rationalised on the basis of physicochemical and structural
characteristics.
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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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B.Barlaam,
R.Ducray,
C.Lambert-van der Brempt,
P.Plé,
C.Bardelle,
N.Brooks,
T.Coleman,
D.Cross,
J.G.Kettle,
and
J.Read
(2011).
Inhibitors of the tyrosine kinase EphB4. Part 4: Discovery and optimization of a benzylic alcohol series.
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Bioorg Med Chem Lett,
21,
2207-2211.
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PDB code:
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B.Mosch,
B.Reissenweber,
C.Neuber,
and
J.Pietzsch
(2010).
Eph receptors and ephrin ligands: important players in angiogenesis and tumor angiogenesis.
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J Oncol,
2010,
135285.
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E.B.Pasquale
(2010).
Eph receptors and ephrins in cancer: bidirectional signalling and beyond.
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Nat Rev Cancer,
10,
165-180.
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G.Martiny-Baron,
P.Holzer,
E.Billy,
C.Schnell,
J.Brueggen,
M.Ferretti,
N.Schmiedeberg,
J.M.Wood,
P.Furet,
and
P.Imbach
(2010).
The small molecule specific EphB4 kinase inhibitor NVP-BHG712 inhibits VEGF driven angiogenesis.
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Angiogenesis,
13,
259-267.
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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.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
