2qj4: Difference between revisions
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<StructureSection load='2qj4' size='340' side='right'caption='[[2qj4]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='2qj4' size='340' side='right'caption='[[2qj4]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2qj4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2qj4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QJ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QJ4 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> | ||
<tr id=' | <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> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qj4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qj4 OCA], [https://pdbe.org/2qj4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qj4 RCSB], [https://www.ebi.ac.uk/pdbsum/2qj4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qj4 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qj4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qj4 OCA], [https://pdbe.org/2qj4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qj4 RCSB], [https://www.ebi.ac.uk/pdbsum/2qj4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qj4 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/HGF_MOUSE HGF_MOUSE] 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:20624990</ref> | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: Daugherty | [[Category: Daugherty J]] | ||
[[Category: Gao | [[Category: Gao C-F]] | ||
[[Category: Gherardi | [[Category: Gherardi E]] | ||
[[Category: Miranti | [[Category: Miranti C]] | ||
[[Category: Tolbert | [[Category: Tolbert WD]] | ||
[[Category: Woude | [[Category: Vande Woude G]] | ||
[[Category: Xe | [[Category: Xe Q]] | ||
[[Category: Xu | [[Category: Xu HE]] | ||
Revision as of 14:33, 30 August 2023
A Mechanistic Basis for Converting a Receptor Tyrosine Kinase Agonist to an AntagonistA Mechanistic Basis for Converting a Receptor Tyrosine Kinase Agonist to an Antagonist
Structural highlights
FunctionHGF_MOUSE 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.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHepatocyte 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. 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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