Genome location: Pf3D7_14_v3:1,892,457..1,895,957(-)
Genome classification: Core
Product Description: M17 leucyl aminopeptidase
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 3.4.11.1 (Leucyl aminopeptidase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Component | GO:0005829 | cytosol |
| Component | GO:0020020 | food vacuole |
| Function | GO:0004177 | aminopeptidase activity |
| Function | GO:0042802 | identical protein binding |
| Function | GO:0046872 | metal ion binding |
| Function | GO:0070006 | metalloaminopeptidase activity |
| Process | GO:0006508 | proteolysis |
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 | 1.06 | 0.59 |
| Trophozoite | expressed | 1.61 | 0.31 |
| Schizont | expressed | 0.24 | 0.85 |
| Gametocyte | expressed | 0.63 | 0.70 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1446200
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: 0.122 | MFS: -3.038 | #Insertions: 0
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1309900)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1309900)
Modification: Disrupted | RMgm-3452
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IL11
"Best" AlphaFill ligand hit: DGZ (n-((2r,3s,6s,18s,21s)-2-amino-18-(4-benzoylbenzyl)-21-carbamoyl-3-hydroxy-6-(naphthalen-2-ylmethyl)-4,7,16,19-tetraoxo-1-phenyl-11,14-dioxa-5,8,17,20-tetraazapentacosan-25-yl)hex-5-ynamide, Local RMSD=0.07) with 3T8W (Global RMSD=0.41)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.4.11.1 | leucyl aminopeptidase | BRENDA SOAP query unsuccessful |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q8IL11 | M17 leucyl aminopeptidase | Plasmodium falciparum (isolate 3D7) | HOGENOM, OMA, OrthoMCL, OrthoMCL BLAST | MLS000031748MLS000032251MLS000035287MLS000068873... |
Ortholog Group (OrthoMCL): OG6_100682
Most Similar Human Ortholog: H0Y9Q1
TM-align score: 0.90 | RMSD: 1.99
Seq Identity: 0.30 | Length: 205 / 605
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000002549 | leucine aminopeptidase 3 |
Protein Length: 605 | Molecular Weight (kDa): 67.821
UniProt ID(s): Q8IL11
PDB ID(s): 3KQX, 3KQZ, 3KR4, 3KR5, 3T8W, 4K3N, 4R6T, 4R76, 4R7M, 4X2T
Isoelectric Point: 8.83
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000819 | Peptidase M17, leucyl aminopeptidase, C-terminal |
| InterPro | IPR011356 | Peptidase M17, leucine aminopeptidase/peptidase B |
| InterPro | IPR023042 | Peptidase M17, leucine aminopeptidase |
| InterPro | IPR043472 | Macro domain-like |
| PFam | PF00883 | Peptidase M17, leucyl aminopeptidase, C-terminal |
| Superfamily | SSF52949 | Macro domain-like |
| Superfamily | SSF53187 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 9 | 26 | 13 | 38 |
| disruptive | 11 | 42 | 14 | 56 |
| missense | 6 | 36 | 14 | 46 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 14 | 54 | 33 | 42 |
| disruptive | 22 | 84 | 39 | 125 |
| missense | 12 | 66 | 30 | 93 |
PlasmoDB Total SNPs: 173
Non-coding: 146 | Synonymous: 19 | Nonsynonymous: 8 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 16286469 | Overexpression of leucyl aminopeptidase in Plasmodium falciparum parasites.Target for the antimalarial activity of bestatin. | Gardiner DL, Trenholme KR, ..., Dalton JP | 10.1074/jbc.M508955200 |
| 17107951 | Characterization of the Plasmodium falciparum M17 leucyl aminopeptidase. Aprotease involved in amino acid regulation with potential for antimalarial drugdevelopment. | Stack CM, Lowther J, ..., Dalton JP | 10.1074/jbc.M609251200 |
| 20133789 | Structure of the Plasmodium falciparum M17 aminopeptidase and significance forthe design of drugs targeting the neutral exopeptidases. | McGowan S, Oellig CA, ..., Whisstock JC | 10.1073/pnas.0911813107 |
| 21136929 | Food vacuole proteome of the malarial parasite Plasmodium falciparum. | Lamarque M, Tastet C, ..., Dubremetz JF | 10.1002/prca.200700112 |
| 28934959 | Selective inhibition of PfA-M1, over PfA-M17, by an amino-benzosuberonederivative blocks malaria parasites development in vitro and in vivo. | Bounaadja L, Schmitt M, ..., Florent I | 10.1186/s12936-017-2032-4 |
| 30212465 | Integrative proteomics and bioinformatic prediction enable a high-confidenceapicoplast proteome in malaria parasites. | Boucher MJ, Ghosh S, ..., Yeh E | 10.1371/journal.pbio.2005895 |
| 33303633 | Active site metals mediate an oligomeric equilibrium in Plasmodium M17aminopeptidases. | Malcolm TR, Belousoff MJ, ..., McGowan S | 10.1074/jbc.RA120.016313 |
| 33536500 | Biochemical and cellular characterisation of the Plasmodium falciparum M1 alanylaminopeptidase (PfM1AAP) and M17 leucyl aminopeptidase (PfM17LAP). | Mathew R, Wunderlich J, ..., Dalton JP | 10.1038/s41598-021-82499-4 |
| 35691342 | A metal ion-dependent conformational switch modulates activity of the PlasmodiumM17 aminopeptidase. | Webb CT, Yang W, ..., McGowan S | 10.1016/j.jbc.2022.102119 |