3hmr: Difference between revisions

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-[[Image:3hmr.png|left|200px]]
-{{STRUCTURE_3hmr|  PDB=3hmr  |  SCENE=  }}
+==Crystal structure of the N-terminal fragment (31-127) of the mouse hepatocyte growth factor/scatter factor==
+<StructureSection load='3hmr' size='340' side='right'caption='[[3hmr]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3hmr]] is a 1 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=3HMR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HMR FirstGlance]. <br>
+</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&#8491;</td></tr>
+<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=3hmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hmr OCA], [https://pdbe.org/3hmr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hmr RCSB], [https://www.ebi.ac.uk/pdbsum/3hmr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hmr ProSAT]</span></td></tr>
+</table>
+== 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 ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hm/3hmr_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=3hmr ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Hepatocyte growth factor (HGF) is an activating ligand of the Met receptor tyrosine kinase, whose activity is essential for normal tissue development and organ regeneration but abnormal activation of Met has been implicated in growth, invasion, and metastasis of many types of solid tumors. HGF has two natural splice variants, NK1 and NK2, which contain the N-terminal domain (N) and the first kringle (K1) or the first two kringle domains of HGF. NK1, which is a Met agonist, forms a head-to-tail dimer complex in crystal structures and mutations in the NK1 dimer interface convert NK1 to a Met antagonist. In contrast, NK2 is a Met antagonist, capable of inhibiting HGF's activity in cell proliferation without clear mechanism. Here we report the crystal structure of NK2, which forms a "closed" monomeric conformation through interdomain interactions between the N- domain and the second kringle domain (K2). Mutations that were designed to open up the NK2 closed conformation by disrupting the N/K2 interface convert NK2 from a Met antagonist to an agonist. Remarkably, this mutated NK2 agonist can be converted back to an antagonist by a mutation that disrupts the NK1/NK1 dimer interface. These results reveal the molecular determinants that regulate the agonist/antagonist properties of HGF NK2 and provide critical insights into the dimerization mechanism that regulates the Met receptor activation by HGF.
-===Crystal structure of the N-terminal fragment (31-127) of the mouse hepatocyte growth factor/scatter factor===
+Structural basis for agonism and antagonism of hepatocyte growth factor.,Tolbert WD, Daugherty-Holtrop J, Gherardi E, Vande Woude G, Xu HE Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13264-9. Epub 2010 Jul 12. PMID:20624990<ref>PMID:20624990</ref>
-{{ABSTRACT_PUBMED_20624990}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3hmr" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-[[3hmr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HMR OCA].
+*[[Hepatocyte growth factor|Hepatocyte growth factor]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:020624990</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Tolbert, W D.]]
+[[Category: Tolbert WD]]
-[[Category: Disulfide bond]]
-[[Category: Glycoprotein]]
-[[Category: Growth factor]]
-[[Category: Hgf/sf]]
-[[Category: Hormone]]
-[[Category: Hormone/growth factor]]
-[[Category: Kringle]]
-[[Category: Pyrrolidone carboxylic acid]]
-[[Category: Serine protease homolog]]