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PDBsum entry 1y91
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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 human cdk2 complexed with a pyrazolo[1,5- a]pyrimidine 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. Gene: cdk2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
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Resolution:
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2.15Å
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R-factor:
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0.201
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R-free:
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0.295
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Authors:
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D.S.Williamson,M.J.Parratt,C.J.Torrance,J.F.Bower,J.D.Moore, C.M.Richardson,P.Dokurno,A.D.Cansfield,G.L.Francis,R.J.Hebdon, R.Howes,P.S.Jackson,A.M.Lockie,J.B.Murray,C.L.Nunns,J.Powles, A.Robertson,A.E.Surgenor
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Key ref:
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D.S.Williamson
et al.
(2005).
Structure-guided design of pyrazolo[1,5-a]pyrimidines as inhibitors of human cyclin-dependent kinase 2.
Bioorg Med Chem Lett,
15,
863-867.
PubMed id:
DOI:
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Date:
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14-Dec-04
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Release date:
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08-Feb-05
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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.
286 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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Bioorg Med Chem Lett
15:863-867
(2005)
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PubMed id:
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Structure-guided design of pyrazolo[1,5-a]pyrimidines as inhibitors of human cyclin-dependent kinase 2.
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D.S.Williamson,
M.J.Parratt,
J.F.Bower,
J.D.Moore,
C.M.Richardson,
P.Dokurno,
A.D.Cansfield,
G.L.Francis,
R.J.Hebdon,
R.Howes,
P.S.Jackson,
A.M.Lockie,
J.B.Murray,
C.L.Nunns,
J.Powles,
A.Robertson,
A.E.Surgenor,
C.J.Torrance.
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ABSTRACT
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The protein structure guided design of a series of pyrazolo[1,5-a]pyrimidines
with high potency for human cyclin-dependent kinase 2 (CDK2) is described. Some
examples were shown to inhibit the growth of human colon tumour cells, were
equipotent for CDK1 and were selective against GSK-3beta and other kinases.
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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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S.Ali,
D.A.Heathcote,
S.H.Kroll,
A.S.Jogalekar,
B.Scheiper,
H.Patel,
J.Brackow,
A.Siwicka,
M.J.Fuchter,
M.Periyasamy,
R.S.Tolhurst,
S.K.Kanneganti,
J.P.Snyder,
D.C.Liotta,
E.O.Aboagye,
A.G.Barrett,
and
R.C.Coombes
(2009).
The development of a selective cyclin-dependent kinase inhibitor that shows antitumor activity.
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Cancer Res,
69,
6208-6215.
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C.Peifer,
and
D.R.Alessi
(2008).
Small-molecule inhibitors of PDK1.
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ChemMedChem,
3,
1810-1838.
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T.O.Fischmann,
A.Hruza,
J.S.Duca,
L.Ramanathan,
T.Mayhood,
W.T.Windsor,
H.V.Le,
T.J.Guzi,
M.P.Dwyer,
K.Paruch,
R.J.Doll,
E.Lees,
D.Parry,
W.Seghezzi,
and
V.Madison
(2008).
Structure-guided discovery of cyclin-dependent kinase inhibitors.
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Biopolymers,
89,
372-379.
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PDB codes:
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F.Marchetti,
K.L.Sayle,
J.Bentley,
W.Clegg,
N.J.Curtin,
J.A.Endicott,
B.T.Golding,
R.J.Griffin,
K.Haggerty,
R.W.Harrington,
V.Mesguiche,
D.R.Newell,
M.E.Noble,
R.J.Parsons,
D.J.Pratt,
L.Z.Wang,
and
I.R.Hardcastle
(2007).
Structure-based design of 2-arylamino-4-cyclohexylmethoxy-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinase 2.
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Org Biomol Chem,
5,
1577-1585.
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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
