PDB 4EQU deposited: 2012-04-19 modified: 2012-12-19
Title Human STK-10 (LOK) kinase domain in DFG-out conformation with inhibitor DSA-7
Authors Hari, S.B., Krishnamurty, R., Larson, E.T., Maly, D.J., Merritt, E.A., Perera, B.G., Ranjitkar, P., Swaney, D.L., Villen, J.
Structure factors resolution 2.0 rfactor 0.223 rfree 0.2464
DPI 0.32 theoretical min: 0.20

Protein kinases are key components of most mammalian signal transduction networks and are therapeutically relevant drug targets. Efforts to study protein kinase function would benefit from new technologies that are able to profile kinases in complex proteomes. Here, we describe active site-directed probes for profiling kinases in whole cell extracts and live cells. These probes contain general ligands that stabilize a specific inactive conformation of the ATP-binding sites of protein kinases, as well as trifluoromethylphenyl diazirine and alkyne moieties that allow covalent modification and enrichment of kinases, respectively. A diverse group of serine/threonine and tyrosine kinases were identified as specific targets of these probes in whole cell extracts. In addition, a number of kinase targets were selectively labeled in live cells. Our chemical proteomics approach should be valuable for interrogating protein kinase active sites in physiologically relevant environments.

J.Am.Chem.Soc. 2012 Nov; 134(46):19017-19025 doi:10.1021/ja306035v

Cross References
Database source Identifier Description
PubMed 23088519 JACSAT
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
4EQU/1 4EQU 1 dimer 0 2 8 4089