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[[Image:1ls5.gif|left|200px]]<br /><applet load="1ls5" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1ls5, resolution 2.80&Aring;" />
'''CRYSTAL STRUCTURE OF PLASMEPSIN IV FROM P. FALCIPARUM IN COMPLEX WITH PEPSTATIN A'''<br />


==Overview==
==Crystal structure of plasmepsin IV from P. falciparum in complex with pepstatin A==
Malaria remains a human disease of global significance and a major cause of high infant mortality in endemic nations. Parasites of the genus Plasmodium cause the disease by degrading human hemoglobin as a source of amino acids for their growth and maturation. Hemoglobin degradation is initiated by aspartic proteases, termed plasmepsins, with a cleavage at the alpha-chain between residues Phe33 and Leu34. Plasmepsin II is one of the four catalytically active plasmepsins that has been identified in the food vacuole of Plasmodium falciparum. Novel crystal structures of uncomplexed plasmepsin II as well as the complex with a potent inhibitor have been refined with data extending to resolution limits of 1.9A and 2.7A, and to R factors of 17% and 18%, respectively. The inhibitor, N-(3-[(2-benzo[1,3]dioxol-5-yl-ethyl)[3-(1-methyl-3-oxo-1,3-dihydro-isoind ol-2-yl)-propionyl]-amino]-1-benzyl-2-(hydroxypropyl)-4-benzyloxy-3,5-dime thoxy-benzamide, belongs to a family of potent non-peptidic inhibitors that have large P1' groups. Such inhibitors could not be modeled into the binding cavity of the structure of plasmepsin II in complex with pepstatin A. Our structures reveal that the binding cavities of the new complex and uncomplexed plasmepsin II are considerably more open than that of the pepstatin A complex, allowing for larger heterocyclic groups in the P1', P2' and P2 positions. Both complexed and uncomplexed plasmepsin II crystallized in space group P2, with one monomer in the asymmetric unit. The structures show extensive interlocking of monomers around the crystallographic axis of symmetry, with areas in excess of 2300A(2) buried at the interface, and a loop of one monomer interacting with the binding cavity of the 2-fold related monomer. Electron density for this loop is only fully ordered in the complexed structure.
<StructureSection load='1ls5' size='340' side='right'caption='[[1ls5]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ls5]] 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]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1jgf 1jgf]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LS5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LS5 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]] 2.8&#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=1ls5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ls5 OCA], [https://pdbe.org/1ls5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ls5 RCSB], [https://www.ebi.ac.uk/pdbsum/1ls5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ls5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PLM4_PLAF7 PLM4_PLAF7] During the asexual blood stage, catalyzes the cleavage of denatured host hemoglobin (Hb) (By similarity). Digestion of host Hb is an essential step which provides the parasite with amino acids for protein synthesis, and regulates osmolarity (Probable).[UniProtKB:Q17SB3]
== 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/ls/1ls5_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=1ls5 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1LS5 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 <scene name='pdbligand=IHN:'>IHN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. This structure supersedes the now removed PDB entry 1JGF. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LS5 OCA].
*[[Plasmepsin|Plasmepsin]]
 
__TOC__
==Reference==
</StructureSection>
Novel uncomplexed and complexed structures of plasmepsin II, an aspartic protease from Plasmodium falciparum., Asojo OA, Gulnik SV, Afonina E, Yu B, Ellman JA, Haque TS, Silva AM, J Mol Biol. 2003 Mar 14;327(1):173-81. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12614616 12614616]
[[Category: Large Structures]]
[[Category: Plasmodium falciparum]]
[[Category: Plasmodium falciparum]]
[[Category: Single protein]]
[[Category: Streptomyces argenteolus subsp. toyonakensis]]
[[Category: Afonina, E.]]
[[Category: Afonina E]]
[[Category: Asojo, O A.]]
[[Category: Asojo OA]]
[[Category: Ellman, J A.]]
[[Category: Ellman JA]]
[[Category: Gulnik, S V.]]
[[Category: Gulnik SV]]
[[Category: Haque, T S.]]
[[Category: Haque TS]]
[[Category: Silva, A M.]]
[[Category: Silva AM]]
[[Category: Yu, B.]]
[[Category: Yu B]]
[[Category: IHN]]
[[Category: eukaryotic aspartic proteinase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:47:51 2008''

Latest revision as of 11:27, 10 April 2024

Crystal structure of plasmepsin IV from P. falciparum in complex with pepstatin ACrystal structure of plasmepsin IV from P. falciparum in complex with pepstatin A

Structural highlights

1ls5 is a 4 chain structure with sequence from Plasmodium falciparum and Streptomyces argenteolus subsp. toyonakensis. This structure supersedes the now removed PDB entry 1jgf. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.8Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PLM4_PLAF7 During the asexual blood stage, catalyzes the cleavage of denatured host hemoglobin (Hb) (By similarity). Digestion of host Hb is an essential step which provides the parasite with amino acids for protein synthesis, and regulates osmolarity (Probable).[UniProtKB:Q17SB3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

1ls5, resolution 2.80Å

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