 |
PDBsum entry 2wqb
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Transferase
|
|
|
Title:
|
|
Structure of the tie2 kinase domain in complex with a thiazolopyrimidine inhibitor
|
|
Structure:
|
|
Angiopoietin-1 receptor. Chain: a. Fragment: kinase domain, residues 802-1124. Synonym: tyrosine-protein kinase receptor tie-2, tie2 kinase, tyrosine-protein kinase receptor tek, tunica interna endothelial cell kinase, p140 tek, htie2. Engineered: yes. Mutation: yes
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
|
|
Resolution:
|
|
|
2.95Å
|
R-factor:
|
0.199
|
R-free:
|
0.259
|
|
|
Authors:
|
|
C.Brassington,J.Breed,D.Buttar,M.Fitzek,C.Forder,L.Hassall, B.R.Hayter,C.D.Jones,R.W.A.Luke,E.Mccall,W.Mccoull,R.Norman, D.Paterson,H.Mcmiken,S.Rowsell,J.A.Tucker
|
|
Key ref:
|
|
R.W.Luke
et al.
(2009).
Novel thienopyrimidine and thiazolopyrimidine kinase inhibitors with activity against Tie-2 in vitro and in vivo.
Bioorg Med Chem Lett,
19,
6670-6674.
PubMed id:
|
|
|
Date:
|
|
|
18-Aug-09
|
Release date:
|
03-Nov-09
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
Q02763
(TIE2_HUMAN) -
Angiopoietin-1 receptor from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
1124 a.a.
289 a.a.*
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
|
|
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.2.7.10.1
- receptor protein-tyrosine kinase.
|
|
|
|
|
|
|
Reaction:
|
|
L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
|
|
|
|
|
|
L-tyrosyl-[protein]
|
+
|
ATP
|
=
|
O-phospho-L-tyrosyl-[protein]
|
+
|
ADP
|
+
|
H(+)
|
|
|
|
|
|
|
|
|
|
|
|
|
Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
| |
|
|
Bioorg Med Chem Lett
19:6670-6674
(2009)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Novel thienopyrimidine and thiazolopyrimidine kinase inhibitors with activity against Tie-2 in vitro and in vivo.
|
|
R.W.Luke,
P.Ballard,
D.Buttar,
L.Campbell,
J.Curwen,
S.C.Emery,
A.M.Griffen,
L.Hassall,
B.R.Hayter,
C.D.Jones,
W.McCoull,
M.Mellor,
M.L.Swain,
J.A.Tucker.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
The SAR and improvement in potency against Tie2 of novel thienopyrimidine and
thiazolopyrimidine kinase inhibitors are reported. The crystal structure of one
of these compounds bound to the Tie-2 kinase domain is consistent with the SAR.
These compounds have moderate potency in cellular assays of Tie-2 inhibition,
good physical properties, DMPK, and show evidence of in vivo inhibition of Tie-2.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Links
