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PDBsum entry 3e8d
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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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Crystal structures of the kinase domain of akt2 in complex with atp- competitive inhibitors
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Structure:
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Rac-beta serine/threonine-protein kinase. Chain: a, b. Fragment: akt2 kinase domain (unp residues 146-480). Synonym: rac-pk-beta, protein kinase akt-2, protein kinase b, beta, pkb beta. Engineered: yes. Mutation: yes. Glycogen synthase kinase-3 beta peptide. Chain: c, d.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: akt2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Synthetic: yes. Other_details: the peptide was chemically synthesized. It is found naturally in human.
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Resolution:
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2.70Å
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R-factor:
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0.214
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R-free:
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0.268
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Authors:
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N.O.Concha,P.A.Elkins,A.Smallwood,P.Ward
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Key ref:
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M.B.Rouse
et al.
(2009).
Aminofurazans as potent inhibitors of AKT kinase.
Bioorg Med Chem Lett,
19,
1508-1511.
PubMed id:
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Date:
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19-Aug-08
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Release date:
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14-Oct-08
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PROCHECK
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Headers
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References
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P31751
(AKT2_HUMAN) -
RAC-beta serine/threonine-protein kinase from Homo sapiens
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Seq:
Struc:
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481 a.a.
316 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 2 residue positions (black
crosses)
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Enzyme class:
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E.C.2.7.11.1
- non-specific serine/threonine 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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Bioorg Med Chem Lett
19:1508-1511
(2009)
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PubMed id:
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Aminofurazans as potent inhibitors of AKT kinase.
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M.B.Rouse,
M.A.Seefeld,
J.D.Leber,
K.C.McNulty,
L.Sun,
W.H.Miller,
S.Zhang,
E.A.Minthorn,
N.O.Concha,
A.E.Choudhry,
M.D.Schaber,
D.A.Heerding.
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ABSTRACT
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AKT inhibitors containing an imidazopyridine aminofurazan scaffold have been
optimized. We have previously disclosed identification of the AKT inhibitor
GSK690693, which has been evaluated in clinical trials in cancer patients.
Herein we describe recent efforts focusing on investigating a distinct region of
this scaffold that have afforded compounds (30 and 32) with comparable activity
profiles to that of GSK690693.
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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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M.Congreve,
and
F.Marshall
(2010).
The impact of GPCR structures on pharmacology and structure-based drug design.
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Br J Pharmacol,
159,
986-996.
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T.McHardy,
J.J.Caldwell,
K.M.Cheung,
L.J.Hunter,
K.Taylor,
M.Rowlands,
R.Ruddle,
A.Henley,
A.de Haven Brandon,
M.Valenti,
T.G.Davies,
L.Fazal,
L.Seavers,
F.I.Raynaud,
S.A.Eccles,
G.W.Aherne,
M.D.Garrett,
and
I.Collins
(2010).
Discovery of 4-amino-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamides as selective, orally active inhibitors of protein kinase B (Akt).
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J Med Chem,
53,
2239-2249.
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PDB codes:
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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
codes are
shown on the right.
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Links
