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New page: left|200px<br /> <applet load="1pfz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pfz, resolution 1.85Å" /> '''PROPLASMEPSIN II FR...
 
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[[Image:1pfz.gif|left|200px]]<br />
<applet load="1pfz" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1pfz, resolution 1.85&Aring;" />
'''PROPLASMEPSIN II FROM PLASMODIUM FALCIPARUM'''<br />


==Overview==
==PROPLASMEPSIN II FROM PLASMODIUM FALCIPARUM==
Proplasmepsin II is the zymogen of plasmepsin II, an aspartic proteinase, used by Plasmodiumfalciparum to digest hemoglobin during the blood stage, of malaria. A large shift between the N-domain and the central and, C-domains of proplasmepsin II opens the active site cleft, preventing the, formation of a functional aspartic proteinase active site. This mode of, inhibition of catalytic activity has not been observed in any other, aspartic proteinase zymogen. Instead of occluding a pre-formed active, site, as in the gastric aspartic proteinase zymogens, the prosegment of, proplasmepsin II interacts extensively with the C-domain and serves as a, 'harness' to keep the domains apart. Disruption of key salt bridges at low, pH may be important in activation.
<StructureSection load='1pfz' size='340' side='right'caption='[[1pfz]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1pfz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PFZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PFZ 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]] 1.85&#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=1pfz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pfz OCA], [https://pdbe.org/1pfz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pfz RCSB], [https://www.ebi.ac.uk/pdbsum/1pfz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pfz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PLM2_PLAFX PLM2_PLAFX] During the asexual blood stage, participates in initial cleavage of native host hemoglobin (Hb) resulting in Hb denaturation (PubMed:11782538, PubMed:15574427, PubMed:8844673). May cleave preferentially denatured hemoglobin that has been cleaved by PMI (PubMed:8844673). Digestion of host Hb is an essential step which provides the parasite with amino acids for protein synthesis, and regulates osmolarity (Probable).<ref>PMID:11782538</ref> <ref>PMID:15574427</ref> <ref>PMID:8844673</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/pf/1pfz_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=1pfz ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Proplasmepsin II is the zymogen of plasmepsin II, an aspartic proteinase used by Plasmodiumfalciparum to digest hemoglobin during the blood stage of malaria. A large shift between the N-domain and the central and C-domains of proplasmepsin II opens the active site cleft, preventing the formation of a functional aspartic proteinase active site. This mode of inhibition of catalytic activity has not been observed in any other aspartic proteinase zymogen. Instead of occluding a pre-formed active site, as in the gastric aspartic proteinase zymogens, the prosegment of proplasmepsin II interacts extensively with the C-domain and serves as a 'harness' to keep the domains apart. Disruption of key salt bridges at low pH may be important in activation.


==About this Structure==
Crystal structure of the novel aspartic proteinase zymogen proplasmepsin II from plasmodium falciparum.,Bernstein NK, Cherney MM, Loetscher H, Ridley RG, James MN Nat Struct Biol. 1999 Jan;6(1):32-7. PMID:9886289<ref>PMID:9886289</ref>
1PFZ is a [[http://en.wikipedia.org/wiki/Single_protein Single protein]] structure of sequence from [[http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]] with GOL as [[http://en.wikipedia.org/wiki/ligand ligand]]. Active as [[http://en.wikipedia.org/wiki/ ]], with EC number [[http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.39 3.4.23.39]]. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1PFZ OCA]].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Crystal structure of the novel aspartic proteinase zymogen proplasmepsin II from plasmodium falciparum., Bernstein NK, Cherney MM, Loetscher H, Ridley RG, James MN, Nat Struct Biol. 1999 Jan;6(1):32-7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9886289 9886289]
</div>
<div class="pdbe-citations 1pfz" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Plasmepsin|Plasmepsin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum]]
[[Category: Plasmodium falciparum]]
[[Category: Single protein]]
[[Category: Bernstein NK]]
[[Category: Bernstein, N.K.]]
[[Category: Cherney MM]]
[[Category: Cherney, M.M.]]
[[Category: James MNG]]
[[Category: James, M.N.G.]]
[[Category: Loetscher H]]
[[Category: Loetscher, H.]]
[[Category: Ridley RG]]
[[Category: Ridley, R.G.]]
[[Category: GOL]]
[[Category: aspartic proteinase zymogen]]
[[Category: aspartyl protease]]
[[Category: glycoprotein]]
[[Category: hemoglobinase]]
[[Category: hydrolase]]
[[Category: malaria]]
 
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