1z8g: Difference between revisions

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-{{Seed}}
-[[Image:1z8g.png|left|200px]]
-<!--
+==Crystal structure of the extracellular region of the transmembrane serine protease hepsin with covalently bound preferred substrate.==
-The line below this paragraph, containing "STRUCTURE_1z8g", creates the "Structure Box" on the page.
+<StructureSection load='1z8g' size='340' side='right'caption='[[1z8g]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1z8g]] 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=1Z8G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z8G FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.55&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0QE:CHLOROMETHANE'>0QE</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=AR7:AMINO{[(4S)-4-AMINO-5,5-DIHYDROXYPENTYL]AMINO}METHANIMINIUM'>AR7</scene></td></tr>
-{{STRUCTURE_1z8g|  PDB=1z8g  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1z8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z8g OCA], [https://pdbe.org/1z8g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z8g RCSB], [https://www.ebi.ac.uk/pdbsum/1z8g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z8g ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/HEPS_HUMAN HEPS_HUMAN] Plays an essential role in cell growth and maintenance of cell morphology. May mediate the activating cleavage of HGF and MST1/HGFL.<ref>PMID:21875933</ref> <ref>PMID:15839837</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/z8/1z8g_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=1z8g ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Hepsin is a membrane-anchored, trypsin-like serine protease with prominent expression in the human liver and tumours of the prostate and ovaries. To better understand the biological functions of hepsin, we identified macromolecular substrates employing a tetrapeptide PS-SCL (positional scanning-synthetic combinatorial library) screen that rapidly determines the P1-P4 substrate specificity. Hepsin exhibited strong preference at the P1 position for arginine over lysine, and favoured threonine, leucine or asparagine at the P2, glutamine or lysine at the P3, and proline or lysine at the P4 position. The relative activity of hepsin toward individual AMC (7-amino-4-methylcoumarin)-tetrapeptides was generally consistent with the overall peptide profiling results derived from the PC-SCL screen. The most active tetrapeptide substrate Ac (acetyl)-KQLR-AMC matched with the activation cleavage site of the hepatocyte growth factor precursor sc-HGF (single-chain HGF), KQLR downward arrowVVNG (where downward arrow denotes the cleavage site), as identified by a database analysis of trypsin-like precursors. X-ray crystallographic studies with KQLR chloromethylketone showed that the KQLR peptide fits well into the substrate-binding cleft of hepsin. This hepsin-processed HGF induced c-Met receptor tyrosine phosphorylation in SKOV-3 ovarian cancer cells, indicating that the hepsin-cleaved HGF is biologically active. Activation cleavage site mutants of sc-HGF with predicted non-preferred sequences, DPGR downward arrowVVNG or KQLQ downward arrowVVNG, were not processed, illustrating that the P4-P1 residues can be important determinants for substrate specificity. In addition to finding macromolecular hepsin substrates, the extracellular inhibitors of the HGF activator, HAI-1 and HAI-2, were potent inhibitors of hepsin activity (IC50 4+/-0.2 nM and 12+/-0.5 nM respectively). Together, our findings suggest that the HGF precursor is a potential in vivo substrate for hepsin in tumours, where hepsin expression is dysregulated and may influence tumorigenesis through inappropriate activation and/or regulation of HGF receptor (c-Met) functions.
-===Crystal structure of the extracellular region of the transmembrane serine protease hepsin with covalently bound preferred substrate.===
+Hepatocyte growth factor is a preferred in vitro substrate for human hepsin, a membrane-anchored serine protease implicated in prostate and ovarian cancers.,Herter S, Piper DE, Aaron W, Gabriele T, Cutler G, Cao P, Bhatt AS, Choe Y, Craik CS, Walker N, Meininger D, Hoey T, Austin RJ Biochem J. 2005 Aug 15;390(Pt 1):125-36. PMID:15839837<ref>PMID:15839837</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<!--
+</div>
-The line below this paragraph, {{ABSTRACT_PUBMED_15839837}}, adds the Publication Abstract to the page
+<div class="pdbe-citations 1z8g" style="background-color:#fffaf0;"></div>
-(as it appears on PubMed at http://www.pubmed.gov), where 15839837 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_15839837}}
+__TOC__
+</StructureSection>
-==About this Structure==
-Z8G 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=1Z8G OCA].
-==Reference==
-Hepatocyte growth factor is a preferred in vitro substrate for human hepsin, a membrane-anchored serine protease implicated in prostate and ovarian cancers., Herter S, Piper DE, Aaron W, Gabriele T, Cutler G, Cao P, Bhatt AS, Choe Y, Craik CS, Walker N, Meininger D, Hoey T, Austin RJ, Biochem J. 2005 Aug 15;390(Pt 1):125-36. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15839837 15839837]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Aaron, W.]]
+[[Category: Aaron W]]
-[[Category: Austin, R J.]]
+[[Category: Austin RJ]]
-[[Category: Bhatt, A S.]]
+[[Category: Bhatt AS]]
-[[Category: Cao, P.]]
+[[Category: Cao P]]
-[[Category: Choe, Y.]]
+[[Category: Choe Y]]
-[[Category: Craik, C S.]]
+[[Category: Craik CS]]
-[[Category: Cutler, G.]]
+[[Category: Cutler G]]
-[[Category: Gabriele, T.]]
+[[Category: Gabriele T]]
-[[Category: Herter, S.]]
+[[Category: Herter S]]
-[[Category: Hoey, T.]]
+[[Category: Hoey T]]
-[[Category: Meininger, D.]]
+[[Category: Meininger D]]
-[[Category: Piper, D E.]]
+[[Category: Piper DE]]
-[[Category: Walker, N.]]
+[[Category: Walker N]]
-[[Category: Hydrolase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 09:04:37 2008''