 |
PDBsum entry 4k9y
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transferase/transferase inhibitor
|
PDB id
|
|
|
|
4k9y
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Transferase/transferase inhibitor
|
|
|
Title:
|
|
Focal adhesion kinase catalytic domain in complex with 1-[4-(6-amino- purin-9-yl)-phenyl]-3-(5-tert-butyl-2-p-tolyl-2h-pyrazol-3-yl)-urea
|
|
Structure:
|
|
Focal adhesion kinase 1. Chain: a. Fragment: kinase domain. Synonym: fadk 1, focal adhesion kinase-related nonkinase, frnk, protein phosphatase 1 regulatory subunit 71, ppp1r71, protein- tyrosine kinase 2, p125fak, pp125fak. Engineered: yes
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Gene: ptk2, fak, fak1. Expressed in: trichoplusia ni. Expression_system_taxid: 7111
|
|
Resolution:
|
|
|
2.00Å
|
R-factor:
|
0.165
|
R-free:
|
0.189
|
|
|
Authors:
|
|
D.Musil,U.Graedler,M.Lehmann,T.Heinrich,V.Dresing
|
|
Key ref:
|
|
U.Grädler
et al.
(2013).
Fragment-based discovery of focal adhesion kinase inhibitors.
Bioorg Med Chem Lett,
23,
5401-5409.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
21-Apr-13
|
Release date:
|
11-Sep-13
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
Q05397
(FAK1_HUMAN) -
Focal adhesion kinase 1 from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
1052 a.a.
271 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:
|
Bioorg Med Chem Lett
23:5401-5409
(2013)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Fragment-based discovery of focal adhesion kinase inhibitors.
|
|
U.Grädler,
J.Bomke,
D.Musil,
V.Dresing,
M.Lehmann,
G.Hölzemann,
H.Greiner,
C.Esdar,
M.Krier,
T.Heinrich.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Chemically diverse fragment hits of focal adhesion kinase (FAK) were discovered
by surface plasmon resonance (SPR) screening of our in-house fragment library.
Site specific binding of the primary hits was confirmed in a competition setup
using a high-affinity ATP-site inhibitor of FAK. Protein crystallography
revealed the binding mode of 41 out of 48 selected fragment hits within the
ATP-site. Structural comparison of the fragment binding modes with a DFG-out
inhibitor of FAK initiated first synthetic follow-up optimization leading to
improved binding affinity.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Links
