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Crystal structure of the EphA4 protein tyrosine kinase domain in the apo‐ and dasatinib‐bound state
Author(s) -
Farenc Carine,
Celie Patrick H.N.,
Tensen Cornelis P.,
de Esch Iwan J.P.,
Siegal Gregg
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.10.028
Subject(s) - dasatinib , tyrosine kinase , erythropoietin producing hepatocellular (eph) receptor , receptor tyrosine kinase , ephrin , chemistry , proto oncogene tyrosine protein kinase src , receptor protein tyrosine kinases , sh3 domain , tyrosine , binding site , protein structure , eph receptor a2 , biochemistry , microbiology and biotechnology , kinase , biology , signal transduction
The Eph family of receptor tyrosine kinases regulates diverse cellular processes while the over‐expression of a member of this family, EphA4, has been reported in a variety of malignant carcinomas. To gain insight into molecular mechanisms and to facilitate structure‐based inhibitor design, we solved the crystal structure of the native EphA4 kinase domain in both the apo and dasatinib bound forms. Analysis of the two structures provides insight into structural features of inhibitor binding and revealed a hydrophobic back‐pocket in the ATP‐ binding site of EphA4 which was previously unidentified. The structures suggest a route towards development of novel and specific inhibitors.