1PKG

Structure of a c-Kit Kinase Product Complex

Summary for 1PKG

• Entry DOI: 10.2210/pdb1pkg/pdb
• Descriptor: c-kit protein, MAGNESIUM ION, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: kinase, autophosphorylation, transactivation, transferase activator
• Biological source: Homo sapiens (human); More
• Cellular location: Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Cell membrane; Single-pass type I membrane protein. Isoform 3: Cytoplasm: P10721
• Total number of polymer chains: 2
• Total formula weight: 76009.39

Authors

Mol, C.D.,Lim, K.B.,Sridhar, V.,Zou, H.,Chien, E.Y.T.,Sang, B.-C.,Nowakowski, J.,Kassel, D.B.,Cronin, C.N.,McRee, D.E. (deposition date: 2003-06-05, release date: 2003-08-12, Last modification date: 2024-10-16)

Primary citation

Mol, C.D.,Lim, K.B.,Sridhar, V.,Zou, H.,Chien, E.Y.T.,Sang, B.-C.,Nowakowski, J.,Kassel, D.B.,Cronin, C.N.,McRee, D.E.
Structure of a c-Kit Product Complex Reveals the Basis for Kinase Transactivation.
J.Biol.Chem., 278:31461-31464, 2003

PubMed Abstract: 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.

PubMed: 12824176
DOI: 10.1074/jbc.C300186200

Experimental method

X-RAY DIFFRACTION (2.9 Å)