PF3D7_0808200 (PMX)

Genome location: Pf3D7_08_v3:415,549..419,066(-)

Genome classification: Core

Function and Localization

Product Description: plasmepsin X

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 3.4.23.1 (Pepsin A)

Curated GO (PlasmoDB):

Type	GO Term	Name
Component	GO:0045177	apical part of cell
Component	GO:0044311	exoneme
Function	GO:0004190	aspartic-type endopeptidase activity
Process	GO:0044409	entry into host
Process	GO:0035891	exit from host cell
Process	GO:0006508	proteolysis
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	0.41	0.86
Trophozoite	not expressed	0.03	0.98
Schizont	expressed	0.38	0.86
Gametocyte	expressed	0.10	0.94

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0808200

Resistome Missense Mutations: None

Resistome Compounds with Missense Mutations: None

Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Mutable in CDS

MIS: 1 | MFS: -2.486 | #Insertions: 1

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1222500)

Relative Growth Rate: 0.36 ± 0.32
Confidence: 3.65

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IAS0

"Best" AlphaFill ligand hit: B3P (2-[3-(2-hydroxy-1,1-dihydroxymethyl-ethylamino)-propylamino]-2-hydroxymethyl-propane-1,3-diol, Local RMSD=0.09) with 3ZKG (Global RMSD=3.21)

BRENDA EC Inhibitors:

EC #	Name	EC Inhibitors
3.4.23.1	pepsin A	I2KCNEDTAPI-3morinbestatinluteolinapigenindaidzeinpeptidespefablocquercetin...

Orthology to BindingDB Entries:

UniProt	Protein Name	Species	Homology Source	BindingDB Ligands
Q8IAS0	Plasmepsin X		HOGENOM, OMA, OrthoDB, OrthoMCL BLAST	CHEMBL5172999CHEMBL5208335CHEMBL5191783CHEMBL5204196...
Q8ILG2	Plasmepsin IX		OrthoDB, OrthoMCL BLAST	CHEMBL5191783CHEMBL5190700CHEMBL5190700CHEMBL5182418...

Orthology Information

Ortholog Group (OrthoMCL): OG6_119797

No human ortholog(s)

Protein Information

Protein Length: 573 | Molecular Weight (kDa): 65.114

UniProt ID(s): Q2KNW1, Q2KNW2, Q2KNW3, Q2KNW4, Q2KNW5, Q2KNW6, Q2KNW7, Q2KNX4, Q2KNX8, Q8IAS0

PDB ID(s): 7RY7, 8DSR

Isoelectric Point: 5.22

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

Genetic Variation

MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:

Homozygous genotype calls only

variant type	common	rare	doubleton	singleton
synonymous	13	20	11	19
disruptive	17	31	13	40
missense	11	18	10	25

Any inclusion in genotype call

variant type	common	rare	doubleton	singleton
synonymous	17	33	18	24
disruptive	26	66	24	87
missense	13	39	18	54

PlasmoDB Total SNPs: 207

Non-coding: 162 | Synonymous: 31 | Nonsynonymous: 12 | Stop Codon: 2

Associated Publications

PMID	Title	Authors	DOI/Link
16267556	A protein interaction network of the malaria parasite Plasmodium falciparum.	LaCount DJ, Vignali M, ..., Hughes RE	10.1038/nature04104
20037583	Transcriptional profiling of growth perturbations of the human malaria parasitePlasmodium falciparum.	Hu G, Cabrera A, ..., Bozdech Z	10.1038/nbt.1597
29074774	Plasmepsins IX and X are essential and druggable mediators of malaria parasiteegress and invasion.	Nasamu AS, Glushakova S, ..., Goldberg DE	10.1126/science.aan1478
32109369	Dual Plasmepsin-Targeting Antimalarial Agents Disrupt Multiple Stages of theMalaria Parasite Life Cycle.	Favuzza P, de Lera Ruiz M, ..., Cowman AF	10.1016/j.chom.2020.02.005
35927261	Maturation and substrate processing topography of the Plasmodium falciparuminvasion/egress protease plasmepsin X.	Mukherjee S, Nguyen S, Sharma E, Goldberg DE	10.1038/s41467-022-32271-7
38386597	Prodomain-driven enzyme dimerization: a pH-dependent autoinhibition mechanismthat controls Plasmodium Sub1 activity before merozoite egress	Martinez M, Bouillon A, ..., Barale J-C	10.1128/mbio.00198-24
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
38179191	Design, synthesis and modelling of photoreactive chemical probes forinvestigating target engagement of plasmepsin IX and X in Plasmodium falciparum	Lisauskaite M, Nixon GL, ..., O'Neill PM	10.1039/d3cb00109a
37974949	Design of Novel Series of Antimalarial PMX Inhibitors with Increased Half-Lifevia Molecular Property Optimization	Sakata K, Lowe MA, ..., de Haro T	10.1021/acsmedchemlett.3c00404