1SM2

Crystal structure of the phosphorylated Interleukin-2 tyrosine kinase catalytic domain

Summary for 1SM2

• Entry DOI: 10.2210/pdb1sm2/pdb
• Descriptor: Tyrosine-protein kinase ITK/TSK, STAUROSPORINE (3 entities in total)
• Functional Keywords: protein kinase, immunology, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane (By similarity): Q08881
• Total number of polymer chains: 2
• Total formula weight: 61141.91

Authors

Brown, K.,Long, J.M.,Vial, S.C.M.,Dedi, N.,Dunster, N.J.,Renwick, S.B.,Tanner, A.J.,Frantz, J.D.,Fleming, M.A.,Cheetham, G.M.T. (deposition date: 2004-03-08, release date: 2004-07-16, Last modification date: 2024-02-14)

Primary citation

Brown, K.,Long, J.M.,Vial, S.C.,Dedi, N.,Dunster, N.J.,Renwick, S.B.,Tanner, A.J.,Frantz, J.D.,Fleming, M.A.,Cheetham, G.M.
Crystal structures of interleukin-2 tyrosine kinase and their implications for the design of selective inhibitors.
J.Biol.Chem., 279:18727-18732, 2004

PubMed Abstract: Interleukin-2 tyrosine kinase, Itk, is an important member of the Tec family of non-receptor tyrosine kinases that play a central role in signaling through antigen receptors such as the T-cell receptor, B-cell receptor, and Fcepsilon. Selective inhibition of Itk may be an important way of modulating many diseases involving heightened or inappropriate activation of the immune system. In addition to an unliganded nonphophorylated Itk catalytic kinase domain, we determined the crystal structures of the phosphorylated and nonphosphorylated kinase domain bound to staurosporine, a potent broad-spectrum kinase inhibitor. These structures are useful for the design of novel, highly potent and selective Itk inhibitors and provide insight into the influence of inhibitor binding and phosphorylation on the conformation of Itk.

PubMed: 14766749
DOI: 10.1074/jbc.M400031200

Experimental method

X-RAY DIFFRACTION (2.3 Å)