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PDBsum entry 2c1a
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Transferase/inhibitor
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PDB id
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2c1a
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Contents |
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* Residue conservation analysis
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PDB id:
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Transferase/inhibitor
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Title:
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Structure of camp-dependent protein kinase complexed with isoquinoline-5-sulfonic acid (2-(2-(4-chlorobenzyloxy)ethylamino) ethyl)amide
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Structure:
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Camp-dependent protein kinase. Chain: a. Synonym: protein kinase a, alpha-catalytic subunit, pka c-alpha. Engineered: yes. Camp-dependent protein kinase inhibitor. Chain: i. Synonym: alpha form, pki-alpha, camp-dependent protein kinase inhibitor, muscle/brain isoform. Engineered: yes
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Source:
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Bos taurus. Organism_taxid: 9913. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Homo sapiens. Organism_taxid: 9606
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Biol. unit:
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Dimer (from PDB file)
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Resolution:
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1.95Å
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R-factor:
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0.176
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R-free:
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0.230
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Authors:
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I.Collins,J.Caldwell,T.Fonseca,A.Donald,V.Bavetsias,L.J.Hunter, M.D.Garrett,M.G.Rowlands,G.W.Aherne,T.G.Davies,V.Berdini, S.J.Woodhead,L.C.A.Seavers,P.G.Wyatt,P.Workman,E.Mcdonald
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Key ref:
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I.Collins
et al.
(2006).
Structure-based design of isoquinoline-5-sulfonamide inhibitors of protein kinase B.
Bioorg Med Chem Lett,
14,
1255-1273.
PubMed id:
DOI:
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Date:
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12-Sep-05
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Release date:
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02-Nov-05
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PROCHECK
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Headers
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References
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Enzyme class:
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Chain A:
E.C.2.7.11.11
- cAMP-dependent 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
14:1255-1273
(2006)
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PubMed id:
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Structure-based design of isoquinoline-5-sulfonamide inhibitors of protein kinase B.
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I.Collins,
J.Caldwell,
T.Fonseca,
A.Donald,
V.Bavetsias,
L.J.Hunter,
M.D.Garrett,
M.G.Rowlands,
G.W.Aherne,
T.G.Davies,
V.Berdini,
S.J.Woodhead,
D.Davis,
L.C.Seavers,
P.G.Wyatt,
P.Workman,
E.McDonald.
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ABSTRACT
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Structure-based drug design of novel isoquinoline-5-sulfonamide inhibitors of
PKB as potential antitumour agents was investigated. Constrained pyrrolidine
analogues that mimicked the bound conformation of linear prototypes were
identified and investigated by co-crystal structure determinations with the
related protein PKA. Detailed variation in the binding modes between inhibitors
with similar overall conformations was observed. Potent PKB inhibitors from this
series inhibited GSK3beta phosphorylation in cellular assays, consistent with
inhibition of PKB kinase activity in cells.
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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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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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X.Zhang,
A.C.Gibbs,
C.H.Reynolds,
M.B.Peters,
and
L.M.Westerhoff
(2010).
Quantum mechanical pairwise decomposition analysis of protein kinase B inhibitors: validating a new tool for guiding drug design.
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J Chem Inf Model,
50,
651-661.
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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
