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| | ==Crystal Structure of the ligand-free inactive Matriptase== | | ==Crystal Structure of the ligand-free inactive Matriptase== |
| - | <StructureSection load='4is5' size='340' side='right' caption='[[4is5]], [[Resolution|resolution]] 1.48Å' scene=''> | + | <StructureSection load='4is5' size='340' side='right'caption='[[4is5]], [[Resolution|resolution]] 1.48Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4is5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IS5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IS5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4is5]] is a 1 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=4IS5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IS5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</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]] 1.48Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4isl|4isl]], [[4isn|4isn]], [[4iso|4iso]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRSS14, SNC19, ST14, TADG15 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4is5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4is5 OCA], [https://pdbe.org/4is5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4is5 RCSB], [https://www.ebi.ac.uk/pdbsum/4is5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4is5 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Matriptase Matriptase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.109 3.4.21.109] </span></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=4is5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4is5 OCA], [http://pdbe.org/4is5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4is5 RCSB], [http://www.ebi.ac.uk/pdbsum/4is5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4is5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ST14_HUMAN ST14_HUMAN]] Defects in ST14 are a cause of ichthyosis autosomal recessive with hypotrichosis (ARIH) [MIM:[http://omim.org/entry/610765 610765]]. ARIH is a skin disorder characterized by congenital ichthyosis associated with the presence of less than the normal amount of hair.<ref>PMID:17273967</ref> | + | [https://www.uniprot.org/uniprot/ST14_HUMAN ST14_HUMAN] Defects in ST14 are a cause of ichthyosis autosomal recessive with hypotrichosis (ARIH) [MIM:[https://omim.org/entry/610765 610765]. ARIH is a skin disorder characterized by congenital ichthyosis associated with the presence of less than the normal amount of hair.<ref>PMID:17273967</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ST14_HUMAN ST14_HUMAN]] Degrades extracellular matrix. Proposed to play a role in breast cancer invasion and metastasis. Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site. | + | [https://www.uniprot.org/uniprot/ST14_HUMAN ST14_HUMAN] Degrades extracellular matrix. Proposed to play a role in breast cancer invasion and metastasis. Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Matriptase|Matriptase]] | + | *[[Matriptase 3D structures|Matriptase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Matriptase]] | + | [[Category: Large Structures]] |
| - | [[Category: Huang, M D]] | + | [[Category: Huang MD]] |
| - | [[Category: Li, R]] | + | [[Category: Li R]] |
| - | [[Category: Yuan, C]] | + | [[Category: Yuan C]] |
| - | [[Category: Zhao, B Y]] | + | [[Category: Zhao BY]] |
| - | [[Category: Beta barrel]]
| + | |
| - | [[Category: Epithelium]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Serine protease]]
| + | |
| Structural highlights
Disease
ST14_HUMAN Defects in ST14 are a cause of ichthyosis autosomal recessive with hypotrichosis (ARIH) [MIM:610765. ARIH is a skin disorder characterized by congenital ichthyosis associated with the presence of less than the normal amount of hair.[1]
Function
ST14_HUMAN Degrades extracellular matrix. Proposed to play a role in breast cancer invasion and metastasis. Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site.
Publication Abstract from PubMed
Matriptase, a type II trans-membrane serine protease of the S1 trypsin-like family, is expressed on the surface of nearly all normal human epithelium and found in biological fluid-like human milk. Matriptase overexpression has been implicated in tumor progression in certain epithelium-derived cancer cells. Matriptase is tightly regulated by its cognate inhibitor hepatocyte growth factor activator inhibitor-1 (HAI-1). It has been demonstrated that the Kunitz domain I (KD1) but not Kunitz domain II (KD2) of HAI-1 is responsible for the inhibitory activity of HAI-1 against matriptase. To investigate the molecular basis of inhibition of matriptase by HAI-1, we solved several crystal structures of matriptase serine protease domain in complex with the fragments of HAI-1. Based on these structures, we found that the binding of KD1 was different from previously predicted binding mode. The P3 arginine residue occupies the S3 specificity pocket of matriptase, but not the S4 pocket as in the cases of hepatocyte growth factor activator.HAI-1 KD1 and matriptase.sunflower trypsin inhibitor-1 complexes. The long 60-loop of matriptase makes direct contact with HAI-1 but remains flexible even in the complexes, and its apex does not bind with KD1 tightly. The interactions between this unique 60-loop and KD1 may provide an opportunity to increase the specificity and inhibitory activity of KD1 for matriptase. Furthermore, comparison between KD1 and a homology model of HAI-1 KD2 rationalizes the structural basis of why KD1 but not KD2 is responsible for the inhibitory activity of HAI-1 against matriptase.
Crystal structures of matriptase in complex with its inhibitor hepatocyte growth factor activator inhibitor-1.,Zhao B, Yuan C, Li R, Qu D, Huang M, Ngo JC J Biol Chem. 2013 Apr 19;288(16):11155-64. doi: 10.1074/jbc.M113.454611. Epub, 2013 Feb 26. PMID:23443661[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Basel-Vanagaite L, Attia R, Ishida-Yamamoto A, Rainshtein L, Ben Amitai D, Lurie R, Pasmanik-Chor M, Indelman M, Zvulunov A, Saban S, Magal N, Sprecher E, Shohat M. Autosomal recessive ichthyosis with hypotrichosis caused by a mutation in ST14, encoding type II transmembrane serine protease matriptase. Am J Hum Genet. 2007 Mar;80(3):467-77. Epub 2007 Jan 23. PMID:17273967 doi:S0002-9297(07)60095-0
- ↑ Zhao B, Yuan C, Li R, Qu D, Huang M, Ngo JC. Crystal structures of matriptase in complex with its inhibitor hepatocyte growth factor activator inhibitor-1. J Biol Chem. 2013 Apr 19;288(16):11155-64. doi: 10.1074/jbc.M113.454611. Epub, 2013 Feb 26. PMID:23443661 doi:10.1074/jbc.M113.454611
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