Summary
PDB 4KAB deposited: 2013-04-22 modified: 2013-10-09
Title FOCAL ADHESION KINASE CATALYTIC DOMAIN IN COMPLEX WITH 3-Methyl-1,4-dihydro-pyrazolo[4,5-c]pyrazole
Authors Bomke, J., Dresing, V., Esdar, C., Gradler, U., Greiner, H., Heinrich, T., Holzemann, G., Krier, M., Lehmann, M., Musil, D.
Method X-RAY DIFFRACTION
Structure factors resolution 2.71 rfactor 0.1706 rfree 0.2194
DPI 0.82 theoretical min: 0.38
Related PDB Entries 4K8A 4K9Y 4KAO
Citations

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.

Bioorg.Med.Chem.Lett. 2013 Oct; 23(19):5401-5409 doi:10.1016/j.bmcl.2013.07.050

Cross References
Database source Identifier Description
ChEMBL Document CHEMBL2424535
PubMed 23973211 BMCLE8
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
4KAB/1 4KAB 1 monomer 0 1 1 1876
4KAB/2 4KAB 2 monomer 0 1 1 1850