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3cbl
From Proteopedia
| 3cbl, resolution 1.75Å () | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Sites: | , , and | ||||||||
| Ligands: | |||||||||
| Non-Standard Residues: | |||||||||
| Gene: | FES, FPS (Homo sapiens) | ||||||||
| Activity: | Non-specific protein-tyrosine kinase, with EC number 2.7.10.2 | ||||||||
| Domains: | S_TKc, PTKc_Fes, SH2 | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Crystal structure of human feline sarcoma viral oncogene homologue (v-FES) in complex with staurosporine and a consensus peptide
The SH2 domain of cytoplasmic tyrosine kinases can enhance catalytic activity and substrate recognition, but the molecular mechanisms by which this is achieved are poorly understood. We have solved the structure of the prototypic SH2-kinase unit of the human Fes tyrosine kinase, which appears specialized for positive signaling. In its active conformation, the SH2 domain tightly interacts with the kinase N-terminal lobe and positions the kinase alphaC helix in an active configuration through essential packing and electrostatic interactions. This interaction is stabilized by ligand binding to the SH2 domain. Our data indicate that Fes kinase activation is closely coupled to substrate recognition through cooperative SH2-kinase-substrate interactions. Similarly, we find that the SH2 domain of the active Abl kinase stimulates catalytic activity and substrate phosphorylation through a distinct SH2-kinase interface. Thus, the SH2 and catalytic domains of active Fes and Abl pro-oncogenic kinases form integrated structures essential for effective tyrosine kinase signaling.
Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation., Filippakopoulos P, Kofler M, Hantschel O, Gish GD, Grebien F, Salah E, Neudecker P, Kay LE, Turk BE, Superti-Furga G, Pawson T, Knapp S, Cell. 2008 Sep 5;134(5):793-803. PMID:18775312
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
3CBL is a 2 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Filippakopoulos P, Kofler M, Hantschel O, Gish GD, Grebien F, Salah E, Neudecker P, Kay LE, Turk BE, Superti-Furga G, Pawson T, Knapp S. Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation. Cell. 2008 Sep 5;134(5):793-803. PMID:18775312 doi:10.1016/j.cell.2008.07.047
Page seeded by OCA on Tue Feb 17 00:34:10 2009
Categories: Homo sapiens | Non-specific protein-tyrosine kinase | Arrowsmith, C H. | Bountra, C. | Cooper, C. | Delft, F von. | Edwards, A M. | Elkins, J M. | Filippakopoulos, P. | Knapp, S. | Picaud, S S. | SGC, Structural Genomics Consortium. | Salah, E. | Weigelt, J. | Atp-binding | Avian sarcoma | Feline sarcoma virus | Fe | Fujinami | Kinase | Nucleotide-binding | Oncogene | Phosphoprotein | Proto-oncogene | Sgc | Sh2 domain | Structural genomics consortium | Transferase | Tyrosine-protein kinase | V-fe | Viral
