1QCF

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

Summary for 1QCF

• Entry DOI: 10.2210/pdb1qcf/pdb
• Related: 1AD5
• Descriptor: Tyrosine-protein kinase HCK, 1-TER-BUTYL-3-P-TOLYL-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-YLAMINE (3 entities in total)
• Functional Keywords: tyrosine kinase-inhibitor complex, down-regulated kinase, ordered activation loop, tyrosine kinase
• Biological source: Homo sapiens (human)
• Cellular location: Isoform 1: Lysosome. Isoform 2: Cell membrane ; Lipid-anchor . Cytoplasmic vesicle, secretory vesicle: P08631
• Total number of polymer chains: 1
• Total formula weight: 52281.58

Authors

Schindler, T.,Sicheri, F.,Pico, A.,Gazit, A.,Levitzki, A.,Kuriyan, J. (deposition date: 1999-05-04, release date: 1999-06-08, Last modification date: 2024-10-09)

Primary citation

Schindler, T.,Sicheri, F.,Pico, A.,Gazit, A.,Levitzki, A.,Kuriyan, J.
Crystal structure of Hck in complex with a Src family-selective tyrosine kinase inhibitor.
Mol.Cell, 3:639-648, 1999

PubMed 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.

PubMed: 10360180
DOI: 10.1016/S1097-2765(00)80357-3

Experimental method

X-RAY DIFFRACTION (2 Å)