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| | ==Structure of Prostasin in Complex with Aprotinin== | | ==Structure of Prostasin in Complex with Aprotinin== |
| - | <StructureSection load='3gym' size='340' side='right' caption='[[3gym]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='3gym' size='340' side='right'caption='[[3gym]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3gym]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GYM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GYM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3gym]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GYM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GYM FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3eon|3eon]], [[3e1x|3e1x]], [[3fvf|3fvf]], [[3gyl|3gyl]]</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]] 2.8Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hCAP1, PRSS8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3gym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gym OCA], [https://pdbe.org/3gym PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gym RCSB], [https://www.ebi.ac.uk/pdbsum/3gym PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gym ProSAT]</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=3gym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gym OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3gym RCSB], [http://www.ebi.ac.uk/pdbsum/3gym PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> [[http://www.uniprot.org/uniprot/BPT1_BOVIN BPT1_BOVIN]] Inhibits trypsin, kallikrein, chymotrypsin, and plasmin. | + | [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]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gy/3gym_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gy/3gym_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=3gym 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 3gym" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Basic Pancreatic Trypsin Inhibitor|Basic Pancreatic Trypsin Inhibitor]] | + | *[[BPTI 3D structures|BPTI 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | [[Category: Bos taurus]] | | [[Category: Bos taurus]] |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Harris, J L]] | + | [[Category: Large Structures]] |
| - | [[Category: Hornsby, M]] | + | [[Category: Harris JL]] |
| - | [[Category: Lesley, S A]] | + | [[Category: Hornsby M]] |
| - | [[Category: Shipway, A]] | + | [[Category: Lesley SA]] |
| - | [[Category: Spraggon, G]] | + | [[Category: Shipway A]] |
| - | [[Category: Aprotinin]]
| + | [[Category: Spraggon G]] |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Channel activating]]
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| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Glycoprotein]]
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| - | [[Category: Hcap1]]
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| - | [[Category: Hydrolase]]
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| - | [[Category: Hydrolase-inhibitor complex]]
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| - | [[Category: Inhibition]]
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| - | [[Category: Membrane]]
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| - | [[Category: Prostasin]]
| + | |
| - | [[Category: Protease]]
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| - | [[Category: Protease inhibitor]]
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| - | [[Category: Secreted]]
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| - | [[Category: Serine protease]]
| + | |
| - | [[Category: Serine protease inhibitor]]
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| - | [[Category: Transmembrane]]
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| - | [[Category: Zymogen]]
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| 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 or human channel-activating protease 1 has been reported to play a critical role in the regulation of extracellular sodium ion transport via its activation of the epithelial cell sodium channel. Here, the structure of the extracellular portion of the membrane associated serine protease has been solved to high resolution in complex with a nonselective d-FFR chloromethyl ketone inhibitor, in an apo form, in a form where the apo crystal has been soaked with the covalent inhibitor camostat and in complex with the protein inhibitor aprotinin. It was also crystallized in the presence of the divalent cation Ca(+2). Comparison of the structures with each other and with other members of the trypsin-like serine protease family reveals unique structural features of prostasin and a large degree of conformational variation within specificity determining loops. Of particular interest is the S1 subsite loop which opens and closes in response to basic residues or divalent ions, directly binding Ca(+2) cations. This induced fit active site provides a new possible mode of regulation of trypsin-like proteases adapted in particular to extracellular regions with variable ionic concentrations such as the outer membrane layer of the epithelial cell.
Active site conformational changes of prostasin provide a new mechanism of protease regulation by divalent cations.,Spraggon G, Hornsby M, Shipway A, Tully DC, Bursulaya B, Danahay H, Harris JL, Lesley SA Protein Sci. 2009 May;18(5):1081-94. PMID:19388054[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Spraggon G, Hornsby M, Shipway A, Tully DC, Bursulaya B, Danahay H, Harris JL, Lesley SA. Active site conformational changes of prostasin provide a new mechanism of protease regulation by divalent cations. Protein Sci. 2009 May;18(5):1081-94. PMID:19388054 doi:10.1002/pro.118
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