Three-dimensional structure of the tyrosine kinase c-Src.
The structure of a large fragment of the c-Src tyrosine kinase, comprising the regulatory and kinase domains and the carboxy-terminal tall, has been determined at 1.7 A resolution in a closed, inactive state. Interactions among domains, stabilized by binding of the phosphorylated tail to the SH2 domain, lock the molecule in a conformation that simultaneously disrupts the kinase active site and sequesters the binding surfaces of the SH2 and SH3 domains. The structure shows how appropriate cellular signals, or transforming mutations in v-Src, could break these interactions to produce an open, active kinase.
Xu
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Laboratory of Molecular Medicine, Children's Hospital, Boston, Massachusetts 02115, USA.
Harrison
S C
SC
Eck
M J
MJ
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry*; D018909:src Homology Domains
D016392:Proto-Oncogene Proteins pp60(c-src)