 |
PDBsum entry 4acm
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Transferase
|
|
|
Title:
|
|
Cdk2 in complex with 3-amino-6-(4-{[2-(dimethylamino)ethyl]sulfamoyl}- phenyl)-n-pyridin-3-ylpyrazine-2-carboxamide
|
|
Structure:
|
|
Cyclin-dependent kinase 2. Chain: a. Synonym: cell division protein kinase 2, p33 protein kinase. Engineered: yes. Other_details: acetylation at n-terminal methionine
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
|
|
Resolution:
|
|
|
1.63Å
|
R-factor:
|
0.185
|
R-free:
|
0.218
|
|
|
Authors:
|
|
S.Berg,R.Bhat,M.Anderson,M.Bergh,C.Brassington,S.Hellberg,E.Jerning, K.Hogdin,Y.Lo-Alfredsson,J.Neelissen,Y.Nilsson,M.Ormo,P.Soderman, J.Stanway,J.Tucker,S.Von Berg,T.Weigelt,Y.Xue
|
|
Key ref:
|
|
S.Berg
et al.
(2012).
Discovery of novel potent and highly selective glycogen synthase kinase-3β (GSK3β) inhibitors for Alzheimer's disease: design, synthesis, and characterization of pyrazines.
J Med Chem,
55,
9107-9119.
PubMed id:
|
|
|
Date:
|
|
|
16-Dec-11
|
Release date:
|
16-May-12
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
P24941
(CDK2_HUMAN) -
Cyclin-dependent kinase 2 from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
298 a.a.
277 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.2.7.11.22
- cyclin-dependent 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
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
| |
|
|
J Med Chem
55:9107-9119
(2012)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Discovery of novel potent and highly selective glycogen synthase kinase-3β (GSK3β) inhibitors for Alzheimer's disease: design, synthesis, and characterization of pyrazines.
|
|
S.Berg,
M.Bergh,
S.Hellberg,
K.Högdin,
Y.Lo-Alfredsson,
P.Söderman,
S.von Berg,
T.Weigelt,
M.Ormö,
Y.Xue,
J.Tucker,
J.Neelissen,
E.Jerning,
Y.Nilsson,
R.Bhat.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Glycogen synthase kinase-3β, also called tau phosphorylating kinase, is a
proline-directed serine/threonine kinase which was originally identified due to
its role in glycogen metabolism. Active forms of GSK3β localize to pretangle
pathology including dystrophic neuritis and neurofibrillary tangles in
Alzheimer's disease (AD) brain. By using a high throughput screening (HTS)
approach to search for new chemical series and cocrystallization of key
analogues to guide the optimization and synthesis of our pyrazine series, we
have developed highly potent and selective inhibitors showing cellular efficacy
and blood-brain barrier penetrance. The inhibitors are suitable for in vivo
efficacy testing and may serve as a new treatment strategy for Alzheimer's
disease.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Links
