Product Description: plasmepsin II
SignalP Peptide: N/A
# Transmembrane Domains: 1
EC Numbers: 3.4.23.39 (Plasmepsin II)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020020 | food vacuole |
| Component | GO:0005634 | nucleus |
| Function | GO:0004190 | aspartic-type endopeptidase activity |
| Process | GO:0042540 | hemoglobin catabolic process |
| Process | GO:0009410 | response to xenobiotic stimulus |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | expressed | N/A | N/A |
| Ring | expressed | 0.33 | 0.83 |
| Trophozoite | expressed | 0.75 | 0.60 |
| Schizont | expressed | 0.09 | 0.94 |
| Gametocyte | possibly expressed | 0.22 | 0.87 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1408000
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.249 | MFS: -2.666 | #Insertions: 0
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1034400)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I6V3
"Best" AlphaFill ligand hit: CPS (chaps, Local RMSD=0.18) with 7VE0 (Global RMSD=6.50)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.4.23.39 | plasmepsin II | BRENDA SOAP query unsuccessful |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q8IM16 | Plasmepsin IV [1-448] | HOGENOM, OrthoDB, OrthoMCL BLAST | phenyl-substituted sulfonamides, 6dphenyl-substituted sulfonamides, 6eCHEMBL588662US9353089, 117... | |
| O60989 | Plasmepsin IV, putative | Plasmodium vivax | HOGENOM, OrthoDB, OrthoMCL BLAST | CHEMBL575115CHEMBL584189CHEMBL575150CHEMBL584190... |
| P07339 | Cathepsin D | Homo sapiens | OMA, OrthoDB | Statine-like inhibitor AStatine-like inhibitor 14Statine-like inhibitor 15Statine-like inhibitor 16... |
| P07267 | Saccharopepsin | Saccharomyces cerevisiae | OMA | CHEMBL311322CHEMBL83697 |
| P46925 | Plasmepsin II | Plasmodium falciparum | OMA, OrthoMCL BLAST | Statine-like inhibitor AStatine-like inhibitor 14Statine-like inhibitor 15Statine-like inhibitor 16... |
| P14091 | Cathepsin E | OrthoDB | US9242943, 36CHEMBL588662US9353089, 117US9353089, 176... | |
| P00797 | Renin | Homo sapiens | OrthoDB | 2-aminoquinazoline, 3aCGP 38560Renin nonpeptide inhibitor, 2Renin nonpeptide inhibitor, 3... |
| P06281 | Renin-1 | Mus musculus | OrthoDB | CHEMBL318242CHEMBL321937CHEMBL97865CHEMBL98582... |
| Q6DLW5 | Renin | Macaca mulatta | OrthoDB | CHEMBL1276271Aliskiren HemifumarateIMARIKIREN |
| P08424 | Renin | Rattus norvegicus | OrthoDB | CHEMBL357253CHEMBL414795CHEMBL265833CHEMBL412950... |
| P0DJD9 | Pepsin A-5 | Homo sapiens | OrthoDB | CHEMBL326831CHEMBL432424Boc-Phe-His-Leu-CF3-Ile-AmpBoc-Phe-His-Leu-CF3-Ile-Amp... |
| P20142 | Gastricsin | Homo sapiens | OrthoDB | CHEMBL313773CHEMBL418948CHEMBL287423CHEMBL62380... |
| P04073 | Gastricsin | Rattus norvegicus | OrthoDB | CHEMBL28888CHEMBL424222CHEMBL28738 |
| P39898 | Plasmepsin I | Plasmodium falciparum | OrthoMCL BLAST | Statine-like inhibitor AStatine-like inhibitor 14Statine-like inhibitor 15Statine-like inhibitor 16... |
| Q9Y006 | Plasmepsin III | Plasmodium falciparum | OrthoMCL BLAST | KNI-10006 |
Ortholog Group (OrthoMCL): OG6_100536
Most Similar Human Ortholog: P14091
TM-align score: 0.79 | RMSD: 3.02
Seq Identity: 0.31 | Length: 351 / 453
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000117984 | cathepsin D |
| ENSG00000131400 | napsin A aspartic peptidase |
| ENSG00000196188 | cathepsin E |
| ENSG00000250644 | novel protein |
Protein Length: 453 | Molecular Weight (kDa): 51.481
UniProt ID(s): P46925, Q17SC2, Q17SC3, Q17SC5, Q8I6V3
PDB ID(s): 2R9B, 5YIA, 5YIB, 5YIC, 5YID, 5YIE, 7QYH, 7VE0, 7VE2
Isoelectric Point: 5.29
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001461 | Aspartic peptidase A1 family |
| InterPro | IPR001969 | Aspartic peptidase, active site |
| InterPro | IPR021109 | Aspartic peptidase domain superfamily |
| InterPro | IPR033121 | Peptidase family A1 domain |
| InterPro | IPR034164 | Pepsin-like domain |
| PFam | PF00026 | Peptidase family A1 domain |
| Superfamily | SSF50630 | Aspartic peptidase domain superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 7 | 29 | 17 | 31 |
| disruptive | 15 | 34 | 14 | 59 |
| missense | 15 | 34 | 14 | 56 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 10 | 53 | 17 | 37 |
| disruptive | 24 | 56 | 34 | 100 |
| missense | 22 | 53 | 32 | 76 |
PlasmoDB Total SNPs: 93
Non-coding: 71 | Synonymous: 10 | Nonsynonymous: 11 | Stop Codon: 1
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 9886289 | Crystal structure of the novel aspartic proteinase zymogen proplasmepsin II fromplasmodium falciparum. | Bernstein NK, Cherney MM, ..., James MN | 10.1038/4905 |
| 11782538 | Four plasmepsins are active in the Plasmodium falciparum food vacuole, includinga protease with an active-site histidine. | Banerjee R, Liu J, ..., Goldberg DE | 10.1073/pnas.022630099 |
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 12368868 | Sequence of Plasmodium falciparum chromosomes 2, 10, 11 and 14. | Gardner MJ, Shallom SJ, ..., Fraser CM | 10.1038/nature01094 |
| 14709539 | Trafficking of plasmepsin II to the food vacuole of the malaria parasitePlasmodium falciparum. | Klemba M, Beatty W, Gluzman I, Goldberg DE | 10.1083/jcb200307147 |
| 15574427 | Distal substrate interactions enhance plasmepsin activity. | Istvan ES, Goldberg DE | 10.1074/jbc.M412086200 |
| 19237752 | Crystallographic evidence for noncoplanar catalytic aspartic acids in plasmepsinII resides in the Protein Data Bank. | Robbins AH, Dunn BM, Agbandje-McKenna M, McKenna R | 10.1107/S0907444908041632 |
| 21136929 | Food vacuole proteome of the malarial parasite Plasmodium falciparum. | Lamarque M, Tastet C, ..., Dubremetz JF | 10.1002/prca.200700112 |
| 21767524 | The native conformation of plasmepsin II is kinetically trapped at neutral pH. | Xiao H, Dee D, Yada RY | 10.1016/j.abb.2011.06.017 |
| 27818095 | Genetic markers associated with dihydroartemisinin-piperaquine failure inPlasmodium falciparum malaria in Cambodia: a genotype-phenotype associationstudy. | Amato R, Lim P, ..., Fairhurst RM | 10.1016/S1473-3099(16)30409-1 |
| 29720620 | Plasmepsin II-III copy number accounts for bimodal piperaquine resistance amongCambodian Plasmodium falciparum. | Bopp S, Magistrado P, ..., Volkman SK | 10.1038/s41467-018-04104-z |
| 30379851 | Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. | Briquet S, Ourimi A, ..., Vaquero C | 10.1371/journal.pone.0205596 |
| 24900778 | Evaluation of aminohydantoins as a novel class of antimalarial agents | Meyers MJ, Tortorella MD, ..., Chen X | 10.1021/ml400412x |
| 24750632 | Chemical and biological characterization of pectin-like polysaccharides from thebark of the Malian medicinal tree Cola cordifolia | Austarheim I, Christensen BE, ..., Paulsen BS | 10.1016/j.carbpol.2012.03.005 |
| 38304146 | Inhibition of Plasmodium falciparum plasmepsins by drugs targeting HIV-1protease: A way forward for antimalarial drug discovery | Mishra V, Deshmukh A, ..., Bhaumik P | 10.1016/j.crstbi.2024.100128 |
| 37603126 | Potentials of Terpenoids as Inhibitors of Multiple Plasmodium falciparum ProteinDrug Targets | Ishola AA, Adewole KE, Adebayo JO, Balogun EA | 10.1007/s11686-023-00711-z |
| 23465897 | Structural features of two heteroxylan polysaccharide fractions from wheat branwith anti-complementary and antioxidant activities | Hromadkova Z, Paulsen BS, ..., Ebringerova A | 10.1016/j.carbpol.2012.05.021 |
| 26625296 | Structures of plasmepsin II from Plasmodium falciparum in complex with twohydroxyethylamine-based inhibitors | Recacha R, Leitans J, ..., Tars K | 10.1107/S2053230X15022049 |