PF3D7_0513300 (PNP)

Genome location: Pf3D7_05_v3:568,594..570,527(-)

Genome classification: Core

Function and Localization

Product Description: purine nucleoside phosphorylase

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 2.4.2.1 (Purine-nucleoside phosphorylase)

Curated GO (PlasmoDB):

Type	GO Term	Name
Function	GO:0004731	purine-nucleoside phosphorylase activity
Process	GO:0006148	inosine catabolic process
Process	GO:0006152	purine nucleoside 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	0.85
Trophozoite	expressed	1.12	0.46
Schizont	expressed	0.17	0.89
Gametocyte	expressed	0.30	0.83

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0513300

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: -2.123 | #Insertions: 2

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1113000)

Relative Growth Rate: 0.10 ± 0.24
Confidence: 1.00

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PY17X_1114100)

Modification: Disrupted | RMgm-838

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8T9Z7

"Best" AlphaFill ligand hit: CYT (6-aminopyrimidin-2(1h)-one, Local RMSD=0.09) with 5EFO (Global RMSD=2.65)

BRENDA EC Inhibitors:

EC #	Name	EC Inhibitors
2.4.2.1	purine-nucleoside phosphorylase	NEMPCMBEGTA7KPPHgCl2CuSO4AgNO3folateadenineInosineguaninechrysin...

Orthology to BindingDB Entries:

UniProt	Protein Name	Species	Homology Source	BindingDB Ligands
Q2HXR2	Purine nucleoside phosphorylase	Toxoplasma gondii	HOGENOM, OMA, OrthoMCL BLAST	CHEMBL438632
Q8T9Z7	Purine nucleoside phosphorylase	Plasmodium falciparum	OMA, OrthoMCL, OrthoMCL BLAST	Azetidine based compound, 40Azetidine based compound, (+/-) 41Azetidine based compound, (+/-) 42DADMe-ImmH,7...

Orthology Information

Ortholog Group (OrthoMCL): OG6_107525

No human ortholog(s)

Protein Information

Protein Length: 245 | Molecular Weight (kDa): 26.858

UniProt ID(s): Q8I3X4, Q8T9Z7

PDB ID(s): 1NW4, 1Q1G, 1SQ6, 2BSX, 3ENZ, 3FOW, 3PHC, 6AQS, 6AQU, 8W7H

Isoelectric Point: 6.47

Protein Domain Annotations:

Source	Family ID	Description
InterPro	IPR000845	Nucleoside phosphorylase domain
InterPro	IPR035994	Nucleoside phosphorylase superfamily
PFam	PF01048	Nucleoside phosphorylase domain
Superfamily	SSF53167	Nucleoside phosphorylase superfamily

Genetic Variation

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

Homozygous genotype calls only

variant type	common	rare	doubleton	singleton
synonymous	3	10	11	13
disruptive	9	9	4	10
missense	9	9	4	10

Any inclusion in genotype call

variant type	common	rare	doubleton	singleton
synonymous	6	25	11	18
disruptive	10	19	13	31
missense	10	19	10	23

PlasmoDB Total SNPs: 78

Non-coding: 63 | Synonymous: 6 | Nonsynonymous: 9 | Stop Codon: 0

PMID	Title	Authors	DOI/Link
12368867	Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.	Hall N, Pain A, ..., Barrell BG	10.1038/nature01095
14982926	Plasmodium falciparum purine nucleoside phosphorylase: crystal structures,immucillin inhibitors, and dual catalytic function.	Shi W, Ting LM, ..., Schramm VL	10.1074/jbc.C400068200
16267556	A protein interaction network of the malaria parasite Plasmodium falciparum.	LaCount DJ, Vignali M, ..., Hughes RE	10.1038/nature04104
28523625	Identification of a novel putative inhibitor of the Plasmodium falciparum purinenucleoside phosphorylase: exploring the purine salvage pathway to design newantimalarial drugs.	Kagami LP, das Neves GM, ..., Kawano DF	10.1007/s11030-017-9745-8
30602534	Identifying purine nucleoside phosphorylase as the target of quinine usingcellular thermal shift assay	Dziekan JM, Yu H, ..., Nordlund P	10.1126/scitranslmed.aau3174