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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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Crystal structure of pkc alpha in complex with nvp-aeb071
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Structure:
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Protein kinasE C alpha type. Chain: a, b, c. Fragment: kinase domain, unp residues 320-672. Synonym: pkc-alpha, pkc-a. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: prkca, pkca, prkaca. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
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Resolution:
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2.80Å
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R-factor:
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0.196
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R-free:
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0.277
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Authors:
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W.Stark,G.Rummel,A.Strauss,S.W.Cowan-Jacob
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Key ref:
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J.Wagner
et al.
(2009).
Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes.
J Med Chem,
52,
6193-6196.
PubMed id:
DOI:
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Date:
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02-Sep-09
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Release date:
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03-Nov-09
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PROCHECK
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Headers
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References
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P17252
(KPCA_HUMAN) -
Protein kinase C alpha type
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Seq:
Struc:
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672 a.a.
332 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.2.7.11.13
- Protein kinase C.
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Reaction:
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ATP + a protein = ADP + a phosphoprotein
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ATP
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+
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protein
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=
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ADP
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+
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phosphoprotein
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Gene Ontology (GO) functional annotation
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Biological process
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protein phosphorylation
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1 term
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Biochemical function
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transferase activity, transferring phosphorus-containing groups
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4 terms
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DOI no:
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J Med Chem
52:6193-6196
(2009)
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PubMed id:
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Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes.
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J.Wagner,
P.von Matt,
R.Sedrani,
R.Albert,
N.Cooke,
C.Ehrhardt,
M.Geiser,
G.Rummel,
W.Stark,
A.Strauss,
S.W.Cowan-Jacob,
C.Beerli,
G.Weckbecker,
J.P.Evenou,
G.Zenke,
S.Cottens.
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ABSTRACT
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A series of novel maleimide-based inhibitors of protein kinase C (PKC) were
designed, synthesized, and evaluated. AEB071 (1) was found to be a potent,
selective inhibitor of classical and novel PKC isotypes. 1 is a highly efficient
immunomodulator, acting via inhibition of early T cell activation. The binding
mode of maleimides to PKCs, proposed by molecular modeling, was confirmed by
X-ray analysis of 1 bound in the active site of PKCalpha.
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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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J.F.Djung,
R.J.Mears,
C.A.Montalbetti,
T.S.Coulter,
A.Golebiowski,
A.N.Carr,
O.Barker,
K.D.Greis,
S.Zhou,
E.Dolan,
and
G.F.Davis
(2011).
The synthesis and evaluation of indolylureas as PKCĪ± inhibitors.
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Bioorg Med Chem, 19,
2742-2750.
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S.Y.Zhao,
Y.W.Yang,
H.Q.Zhang,
Y.Yue,
and
M.Fan
(2011).
Synthesis and cytotoxicity of novel 3-amino-4-indolylmaleimide derivatives.
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Arch Pharm Res, 34,
519-526.
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J.M.Kovarik,
and
A.Slade
(2010).
Overview of sotrastaurin clinical pharmacokinetics.
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Ther Drug Monit, 32,
540-543.
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M.Matz,
U.Weber,
M.F.Mashreghi,
C.Lorkowski,
J.Ladhoff,
S.Kramer,
H.H.Neumayer,
and
K.Budde
(2010).
Effects of the new immunosuppressive agent AEB071 on human immune cells.
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Nephrol Dial Transplant, 25,
2159-2167.
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P.Workman,
and
I.Collins
(2010).
Probing the Probes: Fitness Factors For Small Molecule Tools.
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Chem Biol, 17,
561-577.
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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.
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Links
