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PDBsum entry 3d14
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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 structure of mouse aurora a (asn186->gly, lys240->arg, met302- >leu) in complex with 1-{5-[2-(thieno[3,2-d]pyrimidin-4-ylamino)- ethyl]- thiazol-2-yl}-3-(3-trifluoromethyl-phenyl)-urea
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Structure:
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Serine/threonine kinase 6. Chain: a. Fragment: aurora a kinase domain, unp residues 116-382. Engineered: yes. Mutation: yes
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Source:
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Mus musculus. Mouse. Organism_taxid: 10090. Gene: aurka, stk6. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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1.90Å
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R-factor:
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0.213
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R-free:
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0.257
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Authors:
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R.A.Elling,S.Baskaran,D.A.Allen,J.D.Oslob,M.J.Romanowski
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Key ref:
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J.D.Oslob
et al.
(2008).
Discovery of a potent and selective aurora kinase inhibitor.
Bioorg Med Chem Lett,
18,
4880-4884.
PubMed id:
DOI:
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Date:
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04-May-08
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Release date:
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26-Aug-08
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PROCHECK
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Headers
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References
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P97477
(AURKA_MOUSE) -
Aurora kinase A from Mus musculus
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Seq:
Struc:
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395 a.a.
262 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 7 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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DOI no:
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Bioorg Med Chem Lett
18:4880-4884
(2008)
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PubMed id:
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Discovery of a potent and selective aurora kinase inhibitor.
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J.D.Oslob,
M.J.Romanowski,
D.A.Allen,
S.Baskaran,
M.Bui,
R.A.Elling,
W.M.Flanagan,
A.D.Fung,
E.J.Hanan,
S.Harris,
S.A.Heumann,
U.Hoch,
J.W.Jacobs,
J.Lam,
C.E.Lawrence,
R.S.McDowell,
M.A.Nannini,
W.Shen,
J.A.Silverman,
M.M.Sopko,
B.T.Tangonan,
J.Teague,
J.C.Yoburn,
C.H.Yu,
M.Zhong,
K.M.Zimmerman,
T.O'Brien,
W.Lew.
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ABSTRACT
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This communication describes the discovery of a novel series of Aurora kinase
inhibitors. Key SAR and critical binding elements are discussed. Some of the
more advanced analogues potently inhibit cellular proliferation and induce
phenotypes consistent with Aurora kinase inhibition. In particular, compound 21
(SNS-314) is a potent and selective Aurora kinase inhibitor that exhibits
significant activity in pre-clinical in vivo tumor models.
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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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A.Yan,
Y.Chong,
L.Wang,
X.Hu,
and
K.Wang
(2011).
Prediction of biological activity of Aurora-A kinase inhibitors by multilinear regression analysis and support vector machine.
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Bioorg Med Chem Lett,
21,
2238-2243.
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B.Zhang,
Y.Li,
H.Zhang,
and
C.Ai
(2010).
3D-QSAR and Molecular Docking Studies on Derivatives of MK-0457, GSK1070916 and SNS-314 as Inhibitors against Aurora B Kinase.
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Int J Mol Sci,
11,
4326-4347.
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J.P.Arbitrario,
B.J.Belmont,
M.J.Evanchik,
W.M.Flanagan,
R.V.Fucini,
S.K.Hansen,
S.O.Harris,
A.Hashash,
U.Hoch,
J.N.Hogan,
A.R.Howlett,
J.W.Jacobs,
J.W.Lam,
S.C.Ritchie,
M.J.Romanowski,
J.A.Silverman,
D.E.Stockett,
J.N.Teague,
K.M.Zimmerman,
and
P.Taverna
(2010).
SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo.
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Cancer Chemother Pharmacol,
65,
707-717.
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M.S.Coumar,
M.T.Tsai,
C.Y.Chu,
B.J.Uang,
W.H.Lin,
C.Y.Chang,
T.Y.Chang,
J.S.Leou,
C.H.Teng,
J.S.Wu,
M.Y.Fang,
C.H.Chen,
J.T.Hsu,
S.Y.Wu,
Y.S.Chao,
and
H.P.Hsieh
(2010).
Identification, SAR studies, and X-ray co-crystallographic analysis of a novel furanopyrimidine aurora kinase A inhibitor.
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ChemMedChem,
5,
255-267.
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PDB code:
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T.Sardon,
T.Cottin,
J.Xu,
A.Giannis,
and
I.Vernos
(2009).
Development and biological evaluation of a novel aurora a kinase inhibitor.
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Chembiochem,
10,
464-478.
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X.Tao,
H.S.Chon,
S.Fu,
J.J.Kavanagh,
and
W.Hu
(2008).
Update on aurora kinase inhibitors in gynecologic malignancies.
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Recent Pat Anticancer Drug Discov,
3,
162-177.
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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
