View source for 3dfl


==Crystal structure of human Prostasin complexed to 4-guanidinobenzoic acid==
<StructureSection load='3dfl' size='340' side='right'caption='[[3dfl]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3dfl]] 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=3DFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DFL 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]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GBS:4-GUANIDINOBENZOIC+ACID'>GBS</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=3dfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dfl OCA], [https://pdbe.org/3dfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dfl RCSB], [https://www.ebi.ac.uk/pdbsum/3dfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dfl 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/df/3dfl_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=3dfl ConSurf].
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== 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<ref>PMID:18922802</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3dfl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Darke PL]]
[[Category: Munshi SK]]
[[Category: Rickert KW]]
[[Category: Su HP]]