The crystal structure of the autoinhibited form of Hck has
been determined at 2.0 Å resolution, in complex with a specific
pyrazolo
pyrimidine-type inhibitor, PP1. The activation segment, a key
regulatory component of the catalytic domain, is unphosphorylated
and is visualized in its entirety. Tyr-416, the site of activating
autophosphorylation in the Src family kinases, is positioned such
that access to the catalytic machinery is blocked. PP1 is bound
at the ATP-binding site of the kinase, and a methylphenyl group
on PP1 is inserted into an adjacent hydrophobic pocket. The enlargement
of this pocket in autoinhibited Src kinases suggests a route toward
the development of inhibitors that are specific for the inactive
forms of these proteins.
Figure
1 
Figure 2
Figure
3 
Figure 4
Figure
5 
Figure 6
Figure
7