Structure of human Fyn kinase domain complexed with staurosporine.
The tyrosine kinase Fyn is a member of the Src kinase family. Besides the role of Fyn in T cell signal transduction in concert with Lck, its excess activity in the brain is involved with conditions such as Alzheimer's and Parkinson's diseases. Therefore, inhibition of Fyn kinase may help counteract these nervous system disorders. Here, we solved the crystal structure of the human Fyn kinase domain complexed with staurosporine, a potent kinase inhibitor, at 2.8 A resolution. Staurosporine binds to the ATP-binding site of Fyn in a similar manner as in the Lck- and Csk-complexes. The small structural differences in the staurosporine-binding and/or -unbinding region among the three kinase domains may help obtaining the selective inhibitors against the respective kinases.
Kinoshita
Takayoshi
T
Department of Biological Science, Graduate School of Science, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan. kinotk@b.s.osakafu-u.ac.jp
Matsubara
Mamoru
M
Ishiguro
Hiroshi
H
Okita
Kouki
K
Tada
Toshiji
T
D000818:Animals; D002460:Cell Line; D018360:Crystallography, X-Ray; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000737:chemistry; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D051076:Proto-Oncogene Proteins c-fyn / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019311:Staurosporine / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D040681:Structural Homology, Protein
D047428:Protein Kinase Inhibitors; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D019311:Staurosporine