2qj2

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{{Seed}}
 
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[[Image:2qj2.png|left|200px]]
 
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==A Mechanistic Basis for Converting a Receptor Tyrosine Kinase Agonist to an Antagonist==
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The line below this paragraph, containing "STRUCTURE_2qj2", creates the "Structure Box" on the page.
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<StructureSection load='2qj2' size='340' side='right'caption='[[2qj2]], [[Resolution|resolution]] 1.81&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2qj2]] is a 2 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QJ2 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.81&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_2qj2| PDB=2qj2 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qj2 OCA], [https://pdbe.org/2qj2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qj2 RCSB], [https://www.ebi.ac.uk/pdbsum/2qj2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qj2 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/HGF_HUMAN HGF_HUMAN] Defects in HGF are the cause of deafness autosomal recessive type 39 (DFNB39) [MIM:[https://omim.org/entry/608265 608265]. A form of profound prelingual sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.<ref>PMID:19576567</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/HGF_HUMAN HGF_HUMAN] Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types. Activating ligand for the receptor tyrosine kinase MET by binding to it and promoting its dimerization.<ref>PMID:15167892</ref> <ref>PMID:20624990</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qj/2qj2_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2qj2 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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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===A Mechanistic Basis for Converting a Receptor Tyrosine Kinase Agonist to an Antagonist===
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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<ref>PMID:17804794</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2qj2" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_17804794}}, adds the Publication Abstract to the page
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*[[Hepatocyte growth factor|Hepatocyte growth factor]]
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(as it appears on PubMed at http://www.pubmed.gov), where 17804794 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_17804794}}
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__TOC__
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</StructureSection>
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==About this Structure==
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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].
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==Reference==
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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]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Daugherty, J.]]
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[[Category: Daugherty J]]
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[[Category: Gao, C F.]]
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[[Category: Gao C-F]]
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[[Category: Gherardi, E.]]
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[[Category: Gherardi E]]
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[[Category: Miranti, C.]]
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[[Category: Miranti C]]
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[[Category: Tolbert, W D.]]
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[[Category: Tolbert WD]]
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[[Category: Woude, G Vande.]]
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[[Category: Vande Woude G]]
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[[Category: Xe, Q.]]
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[[Category: Xe Q]]
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[[Category: Xu, H E.]]
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[[Category: Xu HE]]
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[[Category: Hgf/sf]]
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[[Category: Hormone/growth factor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 20:09:21 2008''
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Current revision

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

PDB ID 2qj2

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