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[[Image:3fns.jpg|left|thumb|300px|Crystal Strcture of the Plasmepsin, [[3fns]]]]
<StructureSection load='' size='350' side='right' caption='Plasmepsin II complex with a potential antimalarial drug (PDB entry [[4cku]])' scene='44/441867/Cv/1'>
{{STRUCTURE_3fns| right| PDB=3fns  |  SCENE= |CAPTION=Plasmepsin witn Zn ions, [[3fns]] }}
== Function ==
[[Plasmepsin]] (Plm) is a hemoglobin-degrading enzyme produced by the plasmodium parasite.  It is an aspartic acid protease having 2 aspartic acid residues in the active site.  Ten Plm isoforms are known which are named Plm I, II, etc and '''Histo-Aspartic Protease (HAP)'''.


[[Plasmepsin]] (Plm) is a hemoglobin-degrading enzyme produced by the plasmodium parasite.  It is a potential target for anti-malaria drugs.  It is an aspartic acid protease having 2 aspartic acid residues in the active site.  Ten Plm isoforms are known which are named Plm I, II, etc and Histo-Aspartic Protease (HAP).  ProPml II exhibits a large shift between its domains which renders the protease inactive.  The images on the left and right  correspond to one representative Plm structure, ''i.e.'' the Plasmepsin from ''Plasmodium falciparum'' ([[3fns]]).
*'''Proplasmepsin II''' exhibits a large shift between its domains which renders the protease inactive<ref>PMID:9886289</ref>.   


<br />
==Relevance ==
{{TOC limit|limit=2}}
Plm is a potential target for anti-malaria drugs<ref>PMID:25719272</ref>.


== 3D Structures of Plasmepsin ==
== Structural highlights ==
<br />
The active site of Plm II contains a <scene name='44/441867/Cv/4'>catalytic dyad of 2 Asp residues which interact with potential antimalarial inhibitor</scene><ref>PMID:24900843</ref>. <scene name='44/441867/Cv/5'>Whole active site</scene>. Water molecules are shown as red spheres.
<br />
</StructureSection>
<br />
==3D structures of plasmepsin==
<br />
<br />


''Update June 2011''
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|


===HAP===
*Histo-Aspartic Protease


[[3fns]] – PfHAP  - ''Plasmodium falciparum''<br />
**[[3fns]], [[3qvc]], [[6kub]], [[6kuc]], [[6kud]] – PfHAP  - ''Plasmodium falciparum''<br />
[[3fnt]] – PfHAP + inhibitor pepstatin<br />
**[[3fnt]] – PfHAP + pepstatin<br />
[[3fnu]] – PfHAP + KNI-10006<br />
**[[3fnu]], [[3qvi]] – PfHAP + inhibitor<br />


===Plm I===
*Plasmepsin I


[[3qrv]] – PfPlm I residues 117-457<br />
**[[3qrv]] – PfPlm I residues 117-457<br />
[[3qs1]] - PfPlm I residues 117-457 + inhibitor
**[[3qs1]] - PfPlm I residues 117-457 + inhibitor


===Plm II===
*Plasmepsin II


[[1lf4]] – PfPlm II<br />
**[[1lf4]] – PfPlm II<br />
[[3f9q]] – PfPlm II (mutant)<br />
**[[3f9q]] – PfPlm II (mutant)<br />
[[2r9b]] – PfPlm II + peptide inhibitor<br />
**[[2r9b]] – PfPlm II + peptide inhibitor<br />
[[1w6h]], [[2bju]], [[1lf2]], [[1lf3]], [[1lee]] – PfPlm II + inhibitor<br />
**[[1w6h]], [[2bju]], [[1lf2]], [[1lf3]], [[1lee]], [[2igx]], [[2igy]], [[4cku]], [[4y6m]], [[4z22]], [[5yia]], [[5yib]], [[5yic]], [[5yid]], [[5yie]], [[7qyh]] – PfPlm II + inhibitor<br />
[[1w6i]], [[1xdh]], [[1xe5]], [[1xe6]], [[1me6]], [[1sme]] – PfPlm II + pepstatin derivative<br />
**[[4ya8]] – PfPlm II (mutant) + inhibitor<br />
[[1m43]] - PfPlm II (mutant)  + pepstatin derivative<br />
**[[7ve0]], [[7ve2]] – PfPlm II + drug<br />
**[[1w6i]], [[1xdh]], [[1xe5]], [[1xe6]], [[1me6]], [[1sme]] – PfPlm II + pepstatin derivative<br />
**[[1m43]] - PfPlm II (mutant)  + pepstatin derivative<br />


===ProPlm II===
*Plasmepsin IV


[[1pfz]] - PfProPlm II<br />
**[[2anl]] – Plm IV + statine derivative – ''Plasmodium malariae''<br />
[[1miq]] – PvProPlm II – ''Plasmodium vivax''<br />
**[[1ls5]] - PfPlm IV + pepstatin derivative<br />
[[1qs8]] - PvPlm  + pepstatin derivative<br />


===Plm IV===
*Plasmepsin V or aspartic protease PM5


[[2anl]] – Plm IV + statine derivative – ''Plasmodium malariae''<br />
**[[6c4g]] – PvPlm V + inhibitor<br />
[[1ls5]] - PfPlm IV + pepstatin derivative<br />
**[[4zl4]] – PvPlm V + transition state analog<br />


*Plasmepsin X
**[[7ry7]] – PvPlm X <br />
**[[7tbc]], [[7tbd]], [[7tbe]], [[8dsr]] – PfPlm X + inhibitor<br />
**[[7tbb]] – PfPlm X <br />
*Proplasmepsin II
**[[1pfz]], [[5bwy]] - PfProPlm II<br />
**[[1miq]] – PvProPlm II – ''Plasmodium vivax''<br />
**[[1qs8]], [[5i70]] - PvPlm II + pepstatin derivative<br />
}}
== References ==
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Alexander Berchansky, Michal Harel, Jaime Prilusky, Joel L. Sussman
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