1pkg: Difference between revisions
New page: left|200px<br /> <applet load="1pkg" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pkg, resolution 2.90Å" /> '''Structure of a c-Ki... |
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[[Image:1pkg.gif|left|200px]]<br /> | [[Image:1pkg.gif|left|200px]]<br /><applet load="1pkg" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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'''Structure of a c-Kit Kinase Product Complex'''<br /> | '''Structure of a c-Kit Kinase Product Complex'''<br /> | ||
==Overview== | ==Overview== | ||
The c-Kit proto-oncogene is a receptor protein-tyrosine kinase associated | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1PKG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG and ADP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 1PKG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=ADP:'>ADP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PKG OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Chien, E | [[Category: Chien, E Y.T.]] | ||
[[Category: Cronin, C | [[Category: Cronin, C N.]] | ||
[[Category: Kassel, D | [[Category: Kassel, D B.]] | ||
[[Category: Lim, K | [[Category: Lim, K B.]] | ||
[[Category: McRee, D | [[Category: McRee, D E.]] | ||
[[Category: Mol, C | [[Category: Mol, C D.]] | ||
[[Category: Nowakowski, J.]] | [[Category: Nowakowski, J.]] | ||
[[Category: Sang, B | [[Category: Sang, B C.]] | ||
[[Category: Sridhar, V.]] | [[Category: Sridhar, V.]] | ||
[[Category: Zou, H.]] | [[Category: Zou, H.]] | ||
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[[Category: transactivation]] | [[Category: transactivation]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:29:50 2008'' | ||
Revision as of 12:29, 21 February 2008
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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.
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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