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1pkg
From Proteopedia
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|PDB= 1pkg |SIZE=350|CAPTION= <scene name='initialview01'>1pkg</scene>, resolution 2.90Å | |PDB= 1pkg |SIZE=350|CAPTION= <scene name='initialview01'>1pkg</scene>, resolution 2.90Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> | + | |LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5'-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pkg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pkg OCA], [http://www.ebi.ac.uk/pdbsum/1pkg PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1pkg RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]], Germ cell tumors OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]], Leukemia, acute myeloid OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]], Mast cell leukemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]], Mastocytosis with associated hematologic disorder OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]], Piebaldism OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Sridhar, V.]] | [[Category: Sridhar, V.]] | ||
[[Category: Zou, H.]] | [[Category: Zou, H.]] | ||
| - | [[Category: ADP]] | ||
| - | [[Category: MG]] | ||
[[Category: autophosphorylation]] | [[Category: autophosphorylation]] | ||
[[Category: kinase]] | [[Category: kinase]] | ||
| Line 42: | Line 40: | ||
[[Category: transactivation]] | [[Category: transactivation]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:00:54 2008'' |
Revision as of 20:00, 30 March 2008
| |||||||
| , resolution 2.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of a c-Kit Kinase Product Complex
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.
About this Structure
1PKG is a Single protein structure of sequence from Homo sapiens. 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
Page seeded by OCA on Sun Mar 30 23:00:54 2008
