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| | ==NK1 FRAGMENT OF HUMAN HEPATOCYTE GROWTH FACTOR== | | ==NK1 FRAGMENT OF HUMAN HEPATOCYTE GROWTH FACTOR== |
| - | <StructureSection load='1bht' size='340' side='right' caption='[[1bht]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='1bht' size='340' side='right'caption='[[1bht]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1bht]] is a 2 chain structure with 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=1BHT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BHT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1bht]] 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=1BHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BHT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1bht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bht OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1bht RCSB], [http://www.ebi.ac.uk/pdbsum/1bht PDBsum]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <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=1bht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bht OCA], [https://pdbe.org/1bht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bht RCSB], [https://www.ebi.ac.uk/pdbsum/1bht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bht ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/HGF_HUMAN HGF_HUMAN]] Defects in HGF are the cause of deafness autosomal recessive type 39 (DFNB39) [MIM:[http://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> | + | [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> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bh/1bht_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bh/1bht_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </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/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </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=1bht ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 1bht" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Godowski, P J]] | + | [[Category: Large Structures]] |
| - | [[Category: Lokker, N A]]
| + | [[Category: De Vos AM]] |
| - | [[Category: Ultsch, M H]]
| + | [[Category: Godowski PJ]] |
| - | [[Category: Vos, A M.De]] | + | [[Category: Lokker NA]] |
| - | [[Category: C-met receptor angonist/ antagonist]] | + | [[Category: Ultsch MH]] |
| - | [[Category: Growth factor]] | + | |
| - | [[Category: Heparin-binding domain]] | + | |
| - | [[Category: Kringle]]
| + | |
| Structural highlights
Disease
HGF_HUMAN Defects in HGF are the cause of deafness autosomal recessive type 39 (DFNB39) [MIM: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.[1]
Function
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.[2] [3]
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 PubMed
BACKGROUND: Hepatocyte growth factor (HGF) is a mitogen for hepatocytes and has also been implicated as an epithelial morphogen in tumor invasion. HGF activates its specific cellular receptor, c-met, through an aggregation mechanism potentiated by heparan sulfate glycosaminoglycans. HGF consists of an N-terminal (N) domain, four kringle domains (the first of which carries receptor-binding determinants), and an inactive serine-protease-like domain. NK1, a naturally occurring fragment of HGF, acts as an antagonist of HGF in the absence of heparin. RESULTS: The N domain of NK1 consists of a central five-stranded antiparallel beta sheet flanked by an alpha helix and a two-stranded beta ribbon. The overall N domain structure in the context of the NK1 fragment is similar to the structure of the isolated domain; two lysines and an arginine residue coordinate a bound sulfate ion. The NK1 kringle domain is homologous to kringle 4 from plasminogen, except that the lysine-binding pocket is altered by the insertion of a glycine residue. Here, a HEPES molecule is bound in the pocket. The asymmetric unit of the crystal contains a 'head-to-tail' NK1 dimer. We use this dimer to propose a model of the NK2 fragment of HGF. CONCLUSIONS: A cluster of exposed lysine and arginine residues in or near the hairpin-loop region of the N domain might form part of the NK1 heparin-binding site. In our NK2 model, both kringle domains pack loosely against the N domain, and a long, positively charged groove lines the interface. This groove might be involved in glycosaminoglycan binding. The HGF receptor-binding determinants are clustered near the binding pocket of the first kringle domain, opposite the N domain.
Crystal structure of the NK1 fragment of human hepatocyte growth factor at 2.0 A resolution.,Ultsch M, Lokker NA, Godowski PJ, de Vos AM Structure. 1998 Nov 15;6(11):1383-93. PMID:9817840[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schultz JM, Khan SN, Ahmed ZM, Riazuddin S, Waryah AM, Chhatre D, Starost MF, Ploplis B, Buckley S, Velasquez D, Kabra M, Lee K, Hassan MJ, Ali G, Ansar M, Ghosh M, Wilcox ER, Ahmad W, Merlino G, Leal SM, Riazuddin S, Friedman TB, Morell RJ. Noncoding mutations of HGF are associated with nonsyndromic hearing loss, DFNB39. Am J Hum Genet. 2009 Jul;85(1):25-39. doi: 10.1016/j.ajhg.2009.06.003. Epub 2009 , Jul 2. PMID:19576567 doi:10.1016/j.ajhg.2009.06.003
- ↑ Stamos J, Lazarus RA, Yao X, Kirchhofer D, Wiesmann C. Crystal structure of the HGF beta-chain in complex with the Sema domain of the Met receptor. EMBO J. 2004 Jun 16;23(12):2325-35. Epub 2004 May 27. PMID:15167892 doi:10.1038/sj.emboj.7600243
- ↑ Tolbert WD, Daugherty-Holtrop J, Gherardi E, Vande Woude G, Xu HE. Structural basis for agonism and antagonism of hepatocyte growth factor. Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13264-9. Epub 2010 Jul 12. PMID:20624990 doi:10.1073/pnas.1005183107
- ↑ Ultsch M, Lokker NA, Godowski PJ, de Vos AM. Crystal structure of the NK1 fragment of human hepatocyte growth factor at 2.0 A resolution. Structure. 1998 Nov 15;6(11):1383-93. PMID:9817840
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