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1qcf

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Revision as of 12:38, 21 February 2008 by OCA (Talk | contribs)
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1qcf, resolution 2.0Å

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CRYSTAL STRUCTURE OF HCK IN COMPLEX WITH A SRC FAMILY-SELECTIVE TYROSINE KINASE INHIBITOR

Overview

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.

About this Structure

1QCF is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

Reference

Crystal structure of Hck in complex with a Src family-selective tyrosine kinase inhibitor., Schindler T, Sicheri F, Pico A, Gazit A, Levitzki A, Kuriyan J, Mol Cell. 1999 May;3(5):639-48. PMID:10360180

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