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| <StructureSection load='4cku' size='450' side='right' caption='Plasmepsin II complex with a potential antimalarial drug (PDB entry [[4cku]])' scene='44/441867/Cv/1'> | | <StructureSection load='' size='450' 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)'''. |
Revision as of 06:45, 16 September 2017
| 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).
- Proplasmepsin II exhibits a large shift between its domains which renders the protease inactive[1].
Relevance
Plm is a potential target for anti-malaria drugs[2].
Structural highlights
The active site of Plm II contains a catalytic dyad of 2 Asp residues which interact with potential antimalarial inhibitor[3]. Whole active site. Water molecules shown as red spheres.
- ↑ 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:https://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:https://dx.doi.org/10.1021/ml4004952
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3D structures of plasmepsin
Updated on 16-September-2017
{"openlevels":0}
- Histo-Aspartic Protease
- Plasmepsin I
- 3qrv – PfPlm I residues 117-457
- 3qs1 - PfPlm I residues 117-457 + inhibitor
- Plasmepsin II
- 1lf4 – PfPlm II
- 3f9q – PfPlm II (mutant)
- 2r9b – PfPlm II + peptide inhibitor
- 1w6h, 2bju, 1lf2, 1lf3, 1lee, 2igx, 2igy, 4cku, 4y6m, 4z22 – PfPlm II + inhibitor
- 4ya8 – PfPlm II (mutant) + inhibitor
- 1w6i, 1xdh, 1xe5, 1xe6, 1me6, 1sme – PfPlm II + pepstatin derivative
- 1m43 - PfPlm II (mutant) + pepstatin derivative
- Plasmepsin IV
- 2anl – Plm IV + statine derivative – Plasmodium malariae
- 1ls5 - PfPlm IV + pepstatin derivative
- Proplasmepsin II
- 1pfz, 5bwy - PfProPlm II
- 1miq – PvProPlm II – Plasmodium vivax
- 1qs8, 5i70 - PvPlm + pepstatin derivative
References
