2qj2
From Proteopedia
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| - | [[Image:2qj2.gif|left|200px]] | + | [[Image:2qj2.gif|left|200px]] |
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| - | '''A Mechanistic Basis for Converting a Receptor Tyrosine Kinase Agonist to an Antagonist''' | + | {{Structure |
| + | |PDB= 2qj2 |SIZE=350|CAPTION= <scene name='initialview01'>2qj2</scene>, resolution 1.81Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= HGF, HPTA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''A Mechanistic Basis for Converting a Receptor Tyrosine Kinase Agonist to an Antagonist''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2QJ2 is a [ | + | 2QJ2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QJ2 OCA]. |
==Reference== | ==Reference== | ||
| - | A mechanistic basis for converting a receptor tyrosine kinase agonist to an antagonist., Tolbert WD, Daugherty J, Gao C, Xie Q, Miranti C, Gherardi E, Woude GV, Xu HE, Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14592-7. Epub 2007 Sep 5. PMID:[http:// | + | A mechanistic basis for converting a receptor tyrosine kinase agonist to an antagonist., Tolbert WD, Daugherty J, Gao C, Xie Q, Miranti C, Gherardi E, Woude GV, Xu HE, Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14592-7. Epub 2007 Sep 5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17804794 17804794] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: hormone/growth factor]] | [[Category: hormone/growth factor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:26:21 2008'' |
Revision as of 16:26, 20 March 2008
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| , resolution 1.81Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | HGF, HPTA (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
A Mechanistic Basis for Converting a Receptor Tyrosine Kinase Agonist to an Antagonist
Contents |
Overview
Hepatocyte growth factor (HGF) activates the Met receptor tyrosine kinase by binding and promoting receptor dimerization. Here we describe a mechanistic basis for designing Met antagonists based on NK1, a natural variant of HGF containing the N-terminal and the first kringle domain. Through detailed biochemical and structural analyses, we demonstrate that both mouse and human NK1 induce Met dimerization via a conserved NK1 dimer interface. Mutations designed to alter the NK1 dimer interface abolish its ability to promote Met dimerization but retain full Met-binding activity. Importantly, these NK1 mutants act as Met antagonists by inhibiting HGF-mediated cell scattering, proliferation, branching, and invasion. The ability to separate the Met-binding activity of NK1 from its Met dimerization activity thus provides a rational basis for designing Met antagonists. This strategy of antagonist design may be applicable for other growth factor receptors by selectively abolishing the receptor activation ability but not the receptor binding of the growth factors.
Disease
Known diseases associated with this structure: Fibromatosis, gingival OMIM:[182530], Noonan syndrome 4 OMIM:[182530]
About this Structure
2QJ2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
A mechanistic basis for converting a receptor tyrosine kinase agonist to an antagonist., Tolbert WD, Daugherty J, Gao C, Xie Q, Miranti C, Gherardi E, Woude GV, Xu HE, Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14592-7. Epub 2007 Sep 5. PMID:17804794
Page seeded by OCA on Thu Mar 20 18:26:21 2008
