1pkg

From Proteopedia

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Revision as of 16:37, 12 November 2007

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spinqualitylabelsall models 1pkg, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Structure of a c-Kit Kinase Product Complex

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The c-Kit proto-oncogene is a receptor protein-tyrosine kinase associated, with several highly malignant human cancers. Upon binding its ligand, stem, cell factor (SCF), c-Kit forms an active dimer that autophosphorylates, itself and activates a signaling cascade that induces cell growth., Disease-causing human mutations that activate SCF-independent constitutive, expression of c-Kit are found in acute myelogenous leukemia, human mast, cell disease, and gastrointestinal stromal tumors. We report on the, phosphorylation state and crystal structure of a c-Kit product complex., The c-Kit structure is in a fully active form, with ordered kinase, activation and phosphate-binding loops. These results provide key insights, into the molecular basis for c-Kit kinase transactivation to assist in the, design of new competitive inhibitors targeting activated mutant forms of, c-Kit that are resistant to current chemotherapy regimes.

Disease

Known diseases associated with this structure: Gastrointestinal stromal tumor, somatic OMIM:[164920], Germ cell tumors OMIM:[164920], Leukemia, acute myeloid OMIM:[164920], Mast cell leukemia OMIM:[164920], Mastocytosis with associated hematologic disorder OMIM:[164920], Piebaldism OMIM:[164920]

About this Structure

1PKG is a Single protein structure of sequence from Homo sapiens with MG and ADP as ligands. Full crystallographic information is available from OCA.

Reference

Structure of a c-kit product complex reveals the basis for kinase transactivation., Mol CD, Lim KB, Sridhar V, Zou H, Chien EY, Sang BC, Nowakowski J, Kassel DB, Cronin CN, McRee DE, J Biol Chem. 2003 Aug 22;278(34):31461-4. Epub 2003 Jun 24. PMID:12824176

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