Molecule Information

General Information of the Molecule (ID: Mol01047)

• Name: Plasmepsin II (PMII) ,Plasmodium falciparum
• Synonyms: PLM II; Aspartic hemoglobinase II; PfAPD; PfPM1; Plasmepsin 2
• Molecule Type: Protein
• Gene Name: PMII
• Sequence:
  MDITVREHDFKHGFIKSNSTFDGLNIDNSKNKKKIQKGFQILYVLLFCSVMCGLFYYVYE
  NVWLQRDNEMNEILKNSEHLTIGFKVENAHDRILKTIKTHKLKNYIKESVNFLNSGLTKT
  NYLGSSNDNIELVDFQNIMFYGDAEVGDNQQPFTFILDTGSANLWVPSVKCTTAGCLTKH
  LYDSSKSRTYEKDGTKVEMNYVSGTVSGFFSKDLVTVGNLSLPYKFIEVIDTNGFEPTYT
  ASTFDGILGLGWKDLSIGSVDPIVVELKNQNKIENALFTFYLPVHDKHTGFLTIGGIEER
  FYEGPLTYEKLNHDLYWQITLDAHVGNIMLEKANCIVDSGTSAITVPTDFLNKMLQNLDV
  IKVPFLPFYVTLCNNSKLPTFEFTSENGKYTLEPEYYLQHIEDVGPGLCMLNIIGLDFPV
  PTFILGDPFMRKYFTVFDYDNHSVGIALAKKNL
• Function: During the asexual blood stage, participates in initial cleavage of native host hemoglobin (Hb) resulting in Hb denaturation. May cleave preferentially denatured hemoglobin that has been cleaved by PMI. Digestion of host Hb is an essential step which provides the parasite with amino acids for protein synthesis, and regulates osmolarity (Probable).
• Uniprot ID: PLM2_PLAFX

Kingdom: N.A.
Phylum: Apicomplexa
Class: Aconoidasida
Order: Haemosporida
Family: Plasmodiidae
Genus: Plasmodium
Species: Plasmodium falciparum

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Piperaquine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Malaria [1]

• Resistant Disease: Malaria [ICD-11: 1F45.0]
• Resistant Drug: Piperaquine
• Molecule Alteration: Missense mutation + Chromosome variation; PfCRT p.F145I+p.G353V+p.I218F + pfpm2 Amplification
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Plasmodium falciparum strains; 5833
• Experiment for Molecule Alteration: PacBio amplicon sequencing assay; Whole genome sequencing assay
• Experiment for Drug Resistance: Piperaquine susceptibility testing assay
• Mechanism Description: Parasites with the Dd2 haplotype and pfpm2 amplification had significantly greater mean log10-transformed piperaquine IC90 compared to Dd2 parasites without pfpm2 amplification (t test, P =.0079). In parasites with newly emerged PfCRT mutations, mean log10-transformed piperaquine IC90 was not significantly different between parasites with or without pfpm2 amplification.

Disease Class: Malaria [1]

• Resistant Disease: Malaria [ICD-11: 1F45.0]
• Resistant Drug: Piperaquine
• Molecule Alteration: Chromosome variation; pfpm2 Amplification+Haplotype
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Plasmodium falciparum strains; 5833
• Experiment for Molecule Alteration: PacBio amplicon sequencing assay; Whole genome sequencing assay
• Experiment for Drug Resistance: Piperaquine susceptibility testing assay
• Mechanism Description: Parasites with the Dd2 haplotype and pfpm2 amplification had significantly greater mean log10-transformed piperaquine IC90 compared to Dd2 parasites without pfpm2 amplification (t test, P?=?.0079).

References

• Ref 1: Distribution and Temporal Dynamics of Plasmodium falciparum Chloroquine Resistance Transporter Mutations Associated With Piperaquine Resistance in Northern Cambodia. J Infect Dis. 2021 Sep 17;224(6):1077-1085. doi: 10.1093/infdis/jiab055.