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PDBsum entry 1h00
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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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Cdk2 in complex with a disubstituted 4, 6-bis anilino pyrimidine cdk4 inhibitor
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Structure:
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Cell division protein kinase 2. Chain: a. Synonym: p33 protein kinase. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
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Resolution:
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1.60Å
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R-factor:
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0.208
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R-free:
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0.242
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Authors:
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J.F.Beattie,G.A.Breault,R.P.A.Ellston,S.Green,P.J.Jewsbury, C.J.Midgley,R.T.Naven,C.A.Minshull,R.A.Pauptit,J.A.Tucker,J.E.Pease
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Key ref:
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J.F.Beattie
et al.
(2003).
Cyclin-dependent kinase 4 inhibitors as a treatment for cancer. Part 1: identification and optimisation of substituted 4,6-bis anilino pyrimidines.
Bioorg Med Chem Lett,
13,
2955-2960.
PubMed id:
DOI:
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Date:
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10-Jun-02
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Release date:
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11-Jul-03
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PROCHECK
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Headers
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References
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P24941
(CDK2_HUMAN) -
Cyclin-dependent kinase 2 from Homo sapiens
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Seq:
Struc:
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298 a.a.
278 a.a.
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Key: |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.2.7.11.22
- cyclin-dependent 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
13:2955-2960
(2003)
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PubMed id:
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Cyclin-dependent kinase 4 inhibitors as a treatment for cancer. Part 1: identification and optimisation of substituted 4,6-bis anilino pyrimidines.
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J.F.Beattie,
G.A.Breault,
R.P.Ellston,
S.Green,
P.J.Jewsbury,
C.J.Midgley,
R.T.Naven,
C.A.Minshull,
R.A.Pauptit,
J.A.Tucker,
J.E.Pease.
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ABSTRACT
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Using a high-throughput screening campaign, we identified the 4,6-bis anilino
pyrimidines as inhibitors of the cyclin-dependent kinase, CDK4. Herein we
describe the further chemical modification and use of X-ray crystallography to
develop potent and selective in vitro inhibitors of CDK4.
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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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X.Deng,
B.Okram,
Q.Ding,
J.Zhang,
Y.Choi,
F.J.Adrián,
A.Wojciechowski,
G.Zhang,
J.Che,
B.Bursulaya,
S.W.Cowan-Jacob,
G.Rummel,
T.Sim,
and
N.S.Gray
(2010).
Expanding the diversity of allosteric bcr-abl inhibitors.
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J Med Chem,
53,
6934-6946.
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D.Lietha,
and
M.J.Eck
(2008).
Crystal structures of the FAK kinase in complex with TAE226 and related bis-anilino pyrimidine inhibitors reveal a helical DFG conformation.
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PLoS ONE,
3,
e3800.
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PDB codes:
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A.T.García-Sosa,
and
R.L.Mancera
(2006).
The effect of a tightly bound water molecule on scaffold diversity in the computer-aided de novo ligand design of CDK2 inhibitors.
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J Mol Model,
12,
422-431.
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G.A.Landrum,
J.E.Penzotti,
and
S.Putta
(2006).
Feature-map vectors: a new class of informative descriptors for computational drug discovery.
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J Comput Aided Mol Des,
20,
751-762.
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J.Sridhar,
N.Akula,
and
N.Pattabiraman
(2006).
Selectivity and potency of cyclin-dependent kinase inhibitors.
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AAPS J,
8,
E204-E221.
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R.I.Feldman,
J.M.Wu,
M.A.Polokoff,
M.J.Kochanny,
H.Dinter,
D.Zhu,
S.L.Biroc,
B.Alicke,
J.Bryant,
S.Yuan,
B.O.Buckman,
D.Lentz,
M.Ferrer,
M.Whitlow,
M.Adler,
S.Finster,
Z.Chang,
and
D.O.Arnaiz
(2005).
Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1.
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J Biol Chem,
280,
19867-19874.
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PDB code:
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C.McInnes,
S.Wang,
S.Anderson,
J.O'Boyle,
W.Jackson,
G.Kontopidis,
C.Meades,
M.Mezna,
M.Thomas,
G.Wood,
D.P.Lane,
and
P.M.Fischer
(2004).
Structural determinants of CDK4 inhibition and design of selective ATP competitive inhibitors.
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Chem Biol,
11,
525-534.
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H.Park,
M.S.Yeom,
and
S.Lee
(2004).
Loop flexibility and solvent dynamics as determinants for the selective inhibition of cyclin-dependent kinase 4: comparative molecular dynamics simulation studies of CDK2 and CDK4.
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Chembiochem,
5,
1662-1672.
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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
