4E93: Crystal Structure Of Human Feline Sarcoma Viral Oncogene Homologue (V- Fes)in Complex With Tae684

The c-Fes protein-tyrosine kinase modulates cellular signaling pathways governing differentiation, the innate immune response, and vasculogenesis. Here, we report the identification of types I and II kinase inhibitors with potent activity against c-Fes both in vitro and in cell-based assays. One of the most potent inhibitors is the previously described anaplastic lymphoma kinase inhibitor TAE684. The crystal structure of TAE684 in complex with the c-Fes SH2-kinase domain showed excellent shape complementarity with the ATP-binding pocket and a key role for the gatekeeper methionine in the inhibitory mechanism. TAE684 and two pyrazolopyrimidines with nanomolar potency against c-Fes in vitro were used to establish a role for this kinase in osteoclastogenesis, illustrating the value of these inhibitors as tool compounds to probe the diverse biological functions associated with this unique kinase.
PDB ID: 4E93Download
MMDB ID: 98896
PDB Deposition Date: 2012/3/20
Updated in MMDB: 2012/05
Experimental Method:
x-ray diffraction
Resolution: 1.84  Å
Source Organism:
Similar Structures:
Biological Unit for 4E93: monomeric; determined by author and by software (PISA)
Molecular Components in 4E93
Label Count Molecule
Protein (1 molecule)
Tyrosine-protein Kinase Fes/fps(Gene symbol: FES)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

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