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| | <StructureSection load='3dfj' size='340' side='right'caption='[[3dfj]], [[Resolution|resolution]] 1.45Å' scene=''> | | <StructureSection load='3dfj' size='340' side='right'caption='[[3dfj]], [[Resolution|resolution]] 1.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3dfj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DFJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DFJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3dfj]] 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=3DFJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DFJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 1.45Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3dfl|3dfl]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRSS8 ([https://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=3dfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dfj OCA], [https://pdbe.org/3dfj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dfj RCSB], [https://www.ebi.ac.uk/pdbsum/3dfj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dfj 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=3dfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dfj OCA], [https://pdbe.org/3dfj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dfj RCSB], [https://www.ebi.ac.uk/pdbsum/3dfj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dfj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/PRSS8_HUMAN PRSS8_HUMAN]] Possesses a trypsin-like cleavage specificity with a preference for poly-basic substrates. Stimulates epithelial sodium channel (ENaC) activity through activating cleavage of the gamma subunits (SCNN1G).<ref>PMID:15246975</ref> <ref>PMID:15474520</ref>
| + | [https://www.uniprot.org/uniprot/PRSS8_HUMAN PRSS8_HUMAN] Possesses a trypsin-like cleavage specificity with a preference for poly-basic substrates. Stimulates epithelial sodium channel (ENaC) activity through activating cleavage of the gamma subunits (SCNN1G).<ref>PMID:15246975</ref> <ref>PMID:15474520</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/df/3dfj_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/df/3dfj_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> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Darke, P L]] | + | [[Category: Darke PL]] |
| - | [[Category: Munshi, S K]] | + | [[Category: Munshi SK]] |
| - | [[Category: Rickert, K W]] | + | [[Category: Rickert KW]] |
| - | [[Category: Su, H P]] | + | [[Category: Su HP]] |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Prostasin]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Serine protease]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Zymogen]]
| + | |
| Structural highlights
Function
PRSS8_HUMAN Possesses a trypsin-like cleavage specificity with a preference for poly-basic substrates. Stimulates epithelial sodium channel (ENaC) activity through activating cleavage of the gamma subunits (SCNN1G).[1] [2]
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
Prostasin (also called channel activating protease-1 (CAP1)) is an extracellular serine protease implicated in the modulation of fluid and electrolyte regulation via proteolysis of the epithelial sodium channel. Several disease states, particularly hypertension, can be affected by modulation of epithelial sodium channel activity. Thus, understanding the biochemical function of prostasin and developing specific agents to inhibit its activity could have a significant impact on a widespread disease. We report the expression of the prostasin proenzyme in Escherichia coli as insoluble inclusion bodies, refolding and activating via proteolytic removal of the N-terminal propeptide. The refolded and activated enzyme was shown to be pure and monomeric, with kinetic characteristics very similar to prostasin expressed from eukaryotic systems. Active prostasin was crystallized, and the structure was determined to 1.45 A resolution. These apoprotein crystals were soaked with nafamostat, allowing the structure of the inhibited acyl-enzyme intermediate structure to be determined to 2.0 A resolution. Comparison of the inhibited and apoprotein forms of prostasin suggest a mechanism of regulation through stabilization of a loop which interferes with substrate recognition.
Structure of human prostasin, a target for the regulation of hypertension.,Rickert KW, Kelley P, Byrne NJ, Diehl RE, Hall DL, Montalvo AM, Reid JC, Shipman JM, Thomas BW, Munshi SK, Darke PL, Su HP J Biol Chem. 2008 Dec 12;283(50):34864-72. Epub 2008 Oct 14. PMID:18922802[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tong Z, Illek B, Bhagwandin VJ, Verghese GM, Caughey GH. Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell line. Am J Physiol Lung Cell Mol Physiol. 2004 Nov;287(5):L928-35. Epub 2004 Jul 9. PMID:15246975 doi:http://dx.doi.org/10.1152/ajplung.00160.2004
- ↑ Shipway A, Danahay H, Williams JA, Tully DC, Backes BJ, Harris JL. Biochemical characterization of prostasin, a channel activating protease. Biochem Biophys Res Commun. 2004 Nov 12;324(2):953-63. PMID:15474520 doi:http://dx.doi.org/10.1016/j.bbrc.2004.09.123
- ↑ Rickert KW, Kelley P, Byrne NJ, Diehl RE, Hall DL, Montalvo AM, Reid JC, Shipman JM, Thomas BW, Munshi SK, Darke PL, Su HP. Structure of human prostasin, a target for the regulation of hypertension. J Biol Chem. 2008 Dec 12;283(50):34864-72. Epub 2008 Oct 14. PMID:18922802 doi:10.1074/jbc.M805262200
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