2qj2: Difference between revisions

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[[Image:2qj2.gif|left|200px]]
{{Seed}}
[[Image:2qj2.png|left|200px]]


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{{STRUCTURE_2qj2|  PDB=2qj2  |  SCENE=  }}  
{{STRUCTURE_2qj2|  PDB=2qj2  |  SCENE=  }}  


'''A Mechanistic Basis for Converting a Receptor Tyrosine Kinase Agonist to an Antagonist'''
===A Mechanistic Basis for Converting a Receptor Tyrosine Kinase Agonist to an Antagonist===




==Overview==
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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.
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{{ABSTRACT_PUBMED_17804794}}


==About this Structure==
==About this Structure==
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[[Category: Hgf/sf]]
[[Category: Hgf/sf]]
[[Category: Hormone/growth factor]]
[[Category: Hormone/growth factor]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 15:02:39 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 20:09:21 2008''

Revision as of 17:09, 28 July 2008

File:2qj2.png

Template:STRUCTURE 2qj2

A Mechanistic Basis for Converting a Receptor Tyrosine Kinase Agonist to an Antagonist

Template:ABSTRACT PUBMED 17804794

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

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