3D7U

Structural basis for the recognition of c-Src by its inactivator Csk

Summary for 3D7U

• Entry DOI: 10.2210/pdb3d7u/pdb
• Related: 3D7T
• Descriptor: Tyrosine-protein kinase CSK, Proto-oncogene tyrosine-protein kinase Src (2 entities in total)
• Functional Keywords: csk c-src tyrosine kinase, atp-binding, kinase, membrane, nucleotide-binding, phosphoprotein, sh2 domain, sh3 domain, transferase, tyrosine-protein kinase, lipoprotein, myristate, proto-oncogene
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm (By similarity): P41240; Cell membrane (By similarity): P00523
• Total number of polymer chains: 4
• Total formula weight: 122851.72

Authors

Levinson, N.M.,Seeliger, M.A.,Cole, P.A.,Kuriyan, J. (deposition date: 2008-05-21, release date: 2008-08-05, Last modification date: 2024-02-21)

Primary citation

Levinson, N.M.,Seeliger, M.A.,Cole, P.A.,Kuriyan, J.
Structural basis for the recognition of c-Src by its inactivator Csk.
Cell(Cambridge,Mass.), 134:124-134, 2008

PubMed Abstract: The catalytic activity of the Src family of tyrosine kinases is suppressed by phosphorylation on a tyrosine residue located near the C terminus (Tyr 527 in c-Src), which is catalyzed by C-terminal Src Kinase (Csk). Given the promiscuity of most tyrosine kinases, it is remarkable that the C-terminal tails of the Src family kinases are the only known targets of Csk. We have determined the crystal structure of a complex between the kinase domains of Csk and c-Src at 2.9 A resolution, revealing that interactions between these kinases position the C-terminal tail of c-Src at the edge of the active site of Csk. Csk cannot phosphorylate substrates that lack this docking mechanism because the conventional substrate binding site used by most tyrosine kinases to recognize substrates is destabilized in Csk by a deletion in the activation loop.

PubMed: 18614016
DOI: 10.1016/j.cell.2008.05.051

Experimental method

X-RAY DIFFRACTION (4.111 Å)