Abstract:
:The crystal structure of the autoinhibited form of Hck has been determined at 2.0 A 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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Schindler T,Sicheri F,Pico A,Gazit A,Levitzki A,Kuriyan Jdoi
10.1016/s1097-2765(00)80357-3subject
Has Abstractpub_date
1999-05-01 00:00:00pages
639-48issue
5eissn
1097-2765issn
1097-4164pii
S1097-2765(00)80357-3journal_volume
3pub_type
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