Plasmepsin: Difference between revisions
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<StructureSection load=' | <StructureSection load='' size='350' side='right' caption='Plasmepsin II complex with a potential antimalarial drug (PDB entry [[4cku]])' scene='44/441867/Cv/1'> | ||
== Function == | == 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 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)'''. | ||
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== Structural highlights == | == Structural highlights == | ||
The active site of Plm II contains a <scene name='44/441867/Cv/ | 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. | ||
</StructureSection> | </StructureSection> | ||
==3D structures of plasmepsin== | ==3D structures of plasmepsin== | ||
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*Histo-Aspartic Protease | *Histo-Aspartic Protease | ||
**[[3fns]], [[3qvc]] – PfHAP - ''Plasmodium falciparum''<br /> | **[[3fns]], [[3qvc]], [[6kub]], [[6kuc]], [[6kud]] – PfHAP - ''Plasmodium falciparum''<br /> | ||
**[[3fnt]] – PfHAP + pepstatin<br /> | **[[3fnt]] – PfHAP + pepstatin<br /> | ||
**[[3fnu]], [[3qvi]] – PfHAP + inhibitor<br /> | **[[3fnu]], [[3qvi]] – PfHAP + inhibitor<br /> | ||
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**[[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]], [[2igx]], [[2igy]], [[4cku]], [[4y6m]], [[4z22]] – PfPlm II + inhibitor<br /> | **[[1w6h]], [[2bju]], [[1lf2]], [[1lf3]], [[1lee]], [[2igx]], [[2igy]], [[4cku]], [[4y6m]], [[4z22]], [[5yia]], [[5yib]], [[5yic]], [[5yid]], [[5yie]], [[7qyh]] – PfPlm II + inhibitor<br /> | ||
**[[4ya8]] – PfPlm II (mutant) + inhibitor<br /> | **[[4ya8]] – PfPlm II (mutant) + inhibitor<br /> | ||
**[[7ve0]], [[7ve2]] – PfPlm II + drug<br /> | |||
**[[1w6i]], [[1xdh]], [[1xe5]], [[1xe6]], [[1me6]], [[1sme]] – PfPlm II + pepstatin derivative<br /> | **[[1w6i]], [[1xdh]], [[1xe5]], [[1xe6]], [[1me6]], [[1sme]] – PfPlm II + pepstatin derivative<br /> | ||
**[[1m43]] - PfPlm II (mutant) + pepstatin derivative<br /> | **[[1m43]] - PfPlm II (mutant) + pepstatin derivative<br /> | ||
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**[[2anl]] – Plm IV + statine derivative – ''Plasmodium malariae''<br /> | **[[2anl]] – Plm IV + statine derivative – ''Plasmodium malariae''<br /> | ||
**[[1ls5]] - PfPlm IV + pepstatin derivative<br /> | **[[1ls5]] - PfPlm IV + pepstatin derivative<br /> | ||
*Plasmepsin V or aspartic protease PM5 | |||
**[[6c4g]] – PvPlm V + inhibitor<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 | *Proplasmepsin II | ||
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**[[1pfz]], [[5bwy]] - PfProPlm II<br /> | **[[1pfz]], [[5bwy]] - PfProPlm II<br /> | ||
**[[1miq]] – PvProPlm II – ''Plasmodium vivax''<br /> | **[[1miq]] – PvProPlm II – ''Plasmodium vivax''<br /> | ||
**[[1qs8]], [[5i70]] - PvPlm | **[[1qs8]], [[5i70]] - PvPlm II + pepstatin derivative<br /> | ||
}} | }} | ||
== References == | == References == | ||
<references/> | <references/> | ||
[[Category:Topic Page]] | [[Category:Topic Page]] | ||
Latest revision as of 12:50, 31 August 2023
FunctionPlasmepsin (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).
RelevancePlm is a potential target for anti-malaria drugs[2]. Structural highlightsThe active site of Plm II contains a [3]. . Water molecules are shown as red spheres. |
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3D structures of plasmepsin3D structures of plasmepsin
Updated on 31-August-2023
ReferencesReferences
- ↑ Bernstein NK, Cherney MM, Loetscher H, Ridley RG, James MN. Crystal structure of the novel aspartic proteinase zymogen proplasmepsin II from plasmodium falciparum. Nat Struct Biol. 1999 Jan;6(1):32-7. PMID:9886289 doi:10.1038/4905
- ↑ Huizing AP, Mondal M, Hirsch AK. Fighting malaria: structure-guided discovery of nonpeptidomimetic plasmepsin inhibitors. J Med Chem. 2015 Jul 9;58(13):5151-63. doi: 10.1021/jm5014133. Epub 2015 Mar 17. PMID:25719272 doi:http://dx.doi.org/10.1021/jm5014133
- ↑ Jaudzems K, Tars K, Maurops G, Ivdra N, Otikovs M, Leitans J, Kanepe-Lapsa I, Domraceva I, Mutule I, Trapencieris P, Blackman MJ, Jirgensons A. Plasmepsin inhibitory activity and structure-guided optimization of a potent hydroxyethylamine-based antimalarial hit. ACS Med Chem Lett. 2014 Jan 13;5(4):373-7. doi: 10.1021/ml4004952. eCollection, 2014 Apr 10. PMID:24900843 doi:http://dx.doi.org/10.1021/ml4004952