View source for 1sme


==PLASMEPSIN II, A HEMOGLOBIN-DEGRADING ENZYME FROM PLASMODIUM FALCIPARUM, IN COMPLEX WITH PEPSTATIN A==
<StructureSection load='1sme' size='340' side='right'caption='[[1sme]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1sme]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum] and [https://en.wikipedia.org/wiki/Streptomyces_argenteolus_subsp._toyonakensis Streptomyces argenteolus subsp. toyonakensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SME OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SME 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]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IVA:ISOVALERIC+ACID'>IVA</scene>, <scene name='pdbligand=STA:STATINE'>STA</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=1sme FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sme OCA], [https://pdbe.org/1sme PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sme RCSB], [https://www.ebi.ac.uk/pdbsum/1sme PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sme 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/sm/1sme_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=1sme ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
Plasmodium falciparum is the major causative agent of malaria, a disease of worldwide importance. Resistance to current drugs such as chloroquine and mefloquine is spreading at an alarming rate, and our antimalarial armamentarium is almost depleted. The malarial parasite encodes two homologous aspartic proteases, plasmepsins I and II, which are essential components of its hemoglobin-degradation pathway and are novel targets for antimalarial drug development. We have determined the crystal structure of recombinant plasmepsin II complexed with pepstatin A. This represents the first reported crystal structure of a protein from P. falciparum. The crystals contain molecules in two different conformations, revealing a remarkable degree of interdomain flexibility of the enzyme. The structure was used to design a series of selective low molecular weight compounds that inhibit both plasmepsin II and the growth of P. falciparum in culture.

Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum.,Silva AM, Lee AY, Gulnik SV, Maier P, Collins J, Bhat TN, Collins PJ, Cachau RE, Luker KE, Gluzman IY, Francis SE, Oksman A, Goldberg DE, Erickson JW Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10034-9. PMID:8816746<ref>PMID:8816746</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 1sme" style="background-color:#fffaf0;"></div>

==See Also==
*[[Plasmepsin|Plasmepsin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum]]
[[Category: Streptomyces argenteolus subsp. toyonakensis]]
[[Category: Erickson JW]]
[[Category: Goldberg DE]]
[[Category: Gulnik SV]]
[[Category: Lee AY]]
[[Category: Silva AM]]