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PDBsum entry 1g5s
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Cell cycle/transferase
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PDB id
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1g5s
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Contents |
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* Residue conservation analysis
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PDB id:
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Cell cycle/transferase
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Title:
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Crystal structure of human cyclin dependent kinase 2 (cdk2) in complex with the inhibitor h717
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Structure:
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Cell division protein kinase 2. Chain: a. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
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Resolution:
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2.61Å
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R-factor:
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0.201
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R-free:
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0.242
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Authors:
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M.K.Dreyer,D.R.Borcherding,J.A.Dumont,N.P.Peet,J.T.Tsay,P.S.Wright, A.J.Bitonti,J.Shen,S.-H.Kim
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Key ref:
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M.K.Dreyer
et al.
(2001).
Crystal structure of human cyclin-dependent kinase 2 in complex with the adenine-derived inhibitor H717.
J Med Chem,
44,
524-530.
PubMed id:
DOI:
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Date:
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02-Nov-00
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Release date:
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02-Nov-01
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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.
275 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.2.7.11.22
- 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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J Med Chem
44:524-530
(2001)
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PubMed id:
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Crystal structure of human cyclin-dependent kinase 2 in complex with the adenine-derived inhibitor H717.
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M.K.Dreyer,
D.R.Borcherding,
J.A.Dumont,
N.P.Peet,
J.T.Tsay,
P.S.Wright,
A.J.Bitonti,
J.Shen,
S.H.Kim.
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ABSTRACT
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Cyclin-dependent kinases (CDKs) are regulatory proteins of the eukaryotic cell
cycle. They act after association with different cyclins, the concentrations of
which vary throughout the progression of the cell cycle. As central mediators of
cell growth, CDKs are potential targets for inhibitory molecules that would
allow disruption of the cell cycle in order to evoke an antiproliferative effect
and may therefore be useful as cancer therapeutics. We synthesized several
inhibitory 2,6,9-trisubstituted purine derivatives and solved the crystal
structure of one of these compounds, H717, in complex with human CDK2 at 2.6 A
resolution. The orientation of the C2-p-diaminocyclohexyl portion of the
inhibitor is strikingly different from those of similar moieties in other
related inhibitor complexes. The N9-cyclopentyl ring fully occupies a space in
the enzyme which is otherwise empty, while the C6-N-aminobenzyl substituent
points out of the ATP-binding site. The structure provides a basis for the
further development of more potent inhibitory drugs.
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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.P.Mazanetz,
and
P.M.Fischer
(2007).
Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases.
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Nat Rev Drug Discov,
6,
464-479.
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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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L.Havlicek,
K.Fuksova,
V.Krystof,
M.Orsag,
B.Vojtesek,
and
M.Strnad
(2005).
8-Azapurines as new inhibitors of cyclin-dependent kinases.
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Bioorg Med Chem,
13,
5399-5407.
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E.De Moliner,
N.R.Brown,
and
L.N.Johnson
(2003).
Alternative binding modes of an inhibitor to two different kinases.
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Eur J Biochem,
270,
3174-3181.
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PDB code:
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M.Knockaert,
P.Greengard,
and
L.Meijer
(2002).
Pharmacological inhibitors of cyclin-dependent kinases.
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Trends Pharmacol Sci,
23,
417-425.
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P.L.Toogood
(2002).
Progress toward the development of agents to modulate the cell cycle.
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Curr Opin Chem Biol,
6,
472-478.
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A.Westwell
(2001).
Novel antitumour molecules.
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Drug Discov Today,
6,
489-491.
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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
