Crystal structures of the Lyn protein tyrosine kinase domain in its Apo- and inhibitor-bound state.
Neal K Williams, Isabelle S Lucet, S Peter Klinken, Evan Ingley, Jamie Rossjohn
Journal of Biological Chemistry | Published : 2009
The Src-family protein-tyrosine kinase (PTK) Lyn is the most important Src-family kinase in B cells, having both inhibitory and stimulatory activity that is dependent on the receptor, ligand, and developmental context of the B cell. An important role for Lyn has been reported in acute myeloid leukemia and chronic myeloid leukemia, as well as certain solid tumors. Although several Src-family inhibitors are available, the development of Lyn-specific inhibitors, or inhibitors with reduced off-target activity to Lyn, has been hampered by the lack of structural data on the Lyn kinase. Here we report the crystal structure of the non-liganded form of Lyn kinase domain, as well as in complex with th..View full abstract