View source for 3e1x


==The Crystal Structure of Apo Prostasin at 1.7 Angstroms Resolution==
<StructureSection load='3e1x' size='340' side='right'caption='[[3e1x]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3e1x]] 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=3E1X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E1X FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</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></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=3e1x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e1x OCA], [https://pdbe.org/3e1x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e1x RCSB], [https://www.ebi.ac.uk/pdbsum/3e1x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e1x ProSAT]</span></td></tr>
</table>
== 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> 
== 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/e1/3e1x_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3e1x ConSurf].
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== 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<ref>PMID:19388054</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Harris JL]]
[[Category: Hornsby M]]
[[Category: Lesley SA]]
[[Category: Shipway A]]
[[Category: Spraggon G]]