 |
PDBsum entry 2pvh
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Transferase
|
|
|
Title:
|
|
Structure-based design of pyrazolo[1,5-a][1,3,5]triazine derivatives as potent inhibitors of protein kinase ck2
|
|
Structure:
|
|
Casein kinase ii subunit alpha. Chain: a. Synonym: ck ii, ck2-alpha, protein kinase ck2 alpha. Engineered: yes. Mutation: yes
|
|
Source:
|
|
Zea mays. Organism_taxid: 4577. Gene: ack2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
|
|
Resolution:
|
|
|
2.20Å
|
R-factor:
|
0.196
|
R-free:
|
0.236
|
|
|
Authors:
|
|
Z.Nie,C.Perretta,P.Erickson,S.Margosiak,R.Almassy,J.Lu,A.Averill, K.M.Yager,S.Chu
|
|
Key ref:
|
|
Z.Nie
et al.
(2007).
Structure-based design, synthesis, and study of pyrazolo[1,5-a][1,3,5]triazine derivatives as potent inhibitors of protein kinase CK2.
Bioorg Med Chem Lett,
17,
4191-4195.
PubMed id:
|
|
|
Date:
|
|
|
09-May-07
|
Release date:
|
13-May-08
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
P28523
(CSK2A_MAIZE) -
Casein kinase II subunit alpha from Zea mays
|
|
|
|
Seq:
Struc:
|
|
|
|
332 a.a.
328 a.a.*
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
*
PDB and UniProt seqs differ
at 2 residue positions (black
crosses)
|
|
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.2.7.11.1
- non-specific serine/threonine protein kinase.
|
|
|
|
|
|
|
Reaction:
|
|
|
1.
|
L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
|
|
2.
|
L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H+
|
|
|
|
|
|
|
L-seryl-[protein]
|
+
|
ATP
|
=
|
O-phospho-L-seryl-[protein]
|
+
|
ADP
|
+
|
H(+)
|
|
|
|
|
|
|
L-threonyl-[protein]
|
+
|
ATP
|
=
|
O-phospho-L-threonyl-[protein]
|
+
|
ADP
|
+
|
H(+)
|
|
|
|
|
|
|
|
|
|
|
|
|
Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
| |
|
|
Bioorg Med Chem Lett
17:4191-4195
(2007)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Structure-based design, synthesis, and study of pyrazolo[1,5-a][1,3,5]triazine derivatives as potent inhibitors of protein kinase CK2.
|
|
Z.Nie,
C.Perretta,
P.Erickson,
S.Margosiak,
R.Almassy,
J.Lu,
A.Averill,
K.M.Yager,
S.Chu.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
The structure-based design, synthesis, and anticancer activity of novel
inhibitors of protein kinase CK2 are described. Using
pyrazolo[1,5-a][1,3,5]triazine as the core scaffold, a structure-guided series
of modifications provided pM inhibitors with microM-level cytotoxic activity in
cell-based assays with prostate and colon cancer cell lines.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
A.Gratz,
C.Götz,
and
J.Jose
(2010).
A CE-based assay for human protein kinase CK2 activity measurement and inhibitor screening.
|
| |
Electrophoresis,
31,
634-640.
|
|
|
|
|
|
|
G.Cozza,
A.Bortolato,
and
S.Moro
(2010).
How druggable is protein kinase CK2?
|
| |
Med Res Rev,
30,
419-462.
|
|
|
|
|
|
|
G.Cozza,
M.Mazzorana,
E.Papinutto,
J.Bain,
M.Elliott,
G.di Maira,
A.Gianoncelli,
M.A.Pagano,
S.Sarno,
M.Ruzzene,
R.Battistutta,
F.Meggio,
S.Moro,
G.Zagotto,
and
L.A.Pinna
(2009).
Quinalizarin as a potent, selective and cell-permeable inhibitor of protein kinase CK2.
|
| |
Biochem J,
421,
387-395.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
I.S.Sandholt,
B.B.Olsen,
B.Guerra,
and
O.G.Issinger
(2009).
Resorufin: a lead for a new protein kinase CK2 inhibitor.
|
| |
Anticancer Drugs,
20,
238-248.
|
|
|
|
|
|
|
M.N.Morshed,
M.Muddassar,
F.A.Pasha,
and
S.J.Cho
(2009).
Pharmacophore identification and validation study of CK2 inhibitors using CoMFA/CoMSIA.
|
| |
Chem Biol Drug Des,
74,
148-158.
|
|
|
|
|
|
|
B.B.Olsen,
T.Rasmussen,
K.Niefind,
and
O.G.Issinger
(2008).
Biochemical characterization of CK2alpha and alpha' paralogues and their derived holoenzymes: evidence for the existence of a heterotrimeric CK2alpha'-holoenzyme forming trimeric complexes.
|
| |
Mol Cell Biochem,
316,
37-47.
|
|
|
|
|
|
|
J.Raaf,
E.Brunstein,
O.G.Issinger,
and
K.Niefind
(2008).
The CK2 alpha/CK2 beta interface of human protein kinase CK2 harbors a binding pocket for small molecules.
|
| |
Chem Biol,
15,
111-117.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
R.Prudent,
V.Moucadel,
M.López-Ramos,
S.Aci,
B.Laudet,
L.Mouawad,
C.Barette,
J.Einhorn,
C.Einhorn,
J.N.Denis,
G.Bisson,
F.Schmidt,
S.Roy,
L.Lafanechere,
J.C.Florent,
and
C.Cochet
(2008).
Expanding the chemical diversity of CK2 inhibitors.
|
| |
Mol Cell Biochem,
316,
71-85.
|
|
|
|
|
|
|
S.Sarno,
and
L.A.Pinna
(2008).
Protein kinase CK2 as a druggable target.
|
| |
Mol Biosyst,
4,
889-894.
|
|
|
|
|
|
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.
|
|
Links
