 |
PDBsum entry 5cf6
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transferase/transferase inhibitor
|
PDB id
|
|
|
|
5cf6
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Transferase/transferase inhibitor
|
|
|
Title:
|
|
Crystal structure of janus kinase 2 in complex with n,n-dicyclopropyl- 10-[(2s)-2,3-dihydroxypropyl]-3-methyl-7-(methylamino)-3,5,8,10- tetraazatricyclo [7.3.0.02,6]dodeca-1(9),2(6),4,7,11-pentaene-11- carboxamide
|
|
Structure:
|
|
Tyrosine-protein kinase jak2. Chain: a, b. Fragment: catalytic domain, unp residues 839-1132. Synonym: janus kinase 2,jak-2. Engineered: yes
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Gene: jak2. Expressed in: escherichia coli. Expression_system_taxid: 562
|
|
Resolution:
|
|
|
2.50Å
|
R-factor:
|
0.187
|
R-free:
|
0.214
|
|
|
Authors:
|
|
J.S.Sack
|
|
Key ref:
|
|
A.C.Hart
et al.
(2015).
Structure-Based Design of Selective Janus Kinase 2 Imidazo[4,5-d]pyrrolo[2,3-b]pyridine Inhibitors.
Acs Med Chem Lett,
6,
845-849.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
08-Jul-15
|
Release date:
|
26-Aug-15
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
O60674
(JAK2_HUMAN) -
Tyrosine-protein kinase JAK2 from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
1132 a.a.
287 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.2.7.10.2
- non-specific 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
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
| |
|
DOI no:
|
Acs Med Chem Lett
6:845-849
(2015)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Structure-Based Design of Selective Janus Kinase 2 Imidazo[4,5-d]pyrrolo[2,3-b]pyridine Inhibitors.
|
|
A.C.Hart,
G.M.Schroeder,
H.Wan,
J.Grebinski,
J.Inghrim,
J.Kempson,
J.Guo,
W.J.Pitts,
J.S.Tokarski,
J.S.Sack,
J.A.Khan,
J.Lippy,
M.V.Lorenzi,
D.You,
T.McDevitt,
R.Vuppugalla,
Y.Zhang,
L.J.Lombardo,
G.L.Trainor,
A.V.Purandare.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Early hit to lead work on a pyrrolopyridine chemotype provided access to
compounds with biochemical and cellular potency against Janus kinase 2 (JAK2).
Structure-based drug design along the extended hinge region of JAK2 led to the
identification of an important H-bond interaction with the side chain of Tyr
931, which improved JAK family selectivity. The 4,5-dimethyl thiazole analogue
18 demonstrated high levels of JAK family selectivity and was identified as a
promising lead for the program.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Links
