PF3D7_0915000 (NDH2)

Genome location: Pf3D7_09_v3:639,648..641,731(-)

Genome classification: Core

Function and Localization

Product Description: type II NADH:ubiquinone oxidoreductase

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 1.6.5.3 (Transferred entry: 7.1.1.2)

Curated GO (PlasmoDB):

Type	GO Term	Name
Component	GO:0005739	mitochondrion
Function	GO:0008137	NADH dehydrogenase (ubiquinone) activity
Function	GO:0003960	NADPH:quinone reductase activity

Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):

Stage	LR class	MCA mean	MCA prop. zeros
Sporozoite	not expressed	N/A	N/A
Ring	not expressed	0.03	0.99
Trophozoite	expressed	0.24	0.84
Schizont	expressed	0.48	0.70
Gametocyte	possibly expressed	0.56	0.69

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0915000

Resistome Missense Mutations: K168I, S513L

Resistome Compounds with Missense Mutations: GNF-Pf-5611

Resistome # Samples with Disruptive Mutations: 7 (3 missense, 3 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Mutable in CDS

MIS: 0.479 | MFS: -1.983 | #Insertions: 1

PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_0816000)

Relative Growth Rate: 0.93 ± 0.09
Confidence: 6.20

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_0816000)

Modification: Disrupted | RMgm-2365

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8I302

"Best" AlphaFill ligand hit: PGR (r-1,2-propanediol, Local RMSD=0.01) with 3KPK (Global RMSD=3.22)

BRENDA EC Inhibitors:

EC #	Name	EC Inhibitors
1.6.5.3	NADH:ubiquinone reductase (H+-translocating)	No BRENDA inhibitors

Orthology to BindingDB Entries:

UniProt	Protein Name	Species	Homology Source	BindingDB Ligands
P95160	Type II NADH:quinone oxidoreductase Ndh		OrthoMCL	CHEMBL5182198CHEMBL5206556CHEMBL5171834CHEMBL5201484...
P95200	Type II NADH:quinone oxidoreductase NdhA		OrthoMCL	CHEMBL5182198CHEMBL5206556CHEMBL5171834CHEMBL5201484...

Orthology Information

Ortholog Group (OrthoMCL): OG6_100512

No human ortholog(s)

Protein Information

Protein Length: 533 | Molecular Weight (kDa): 61.67

UniProt ID(s): Q8I302

PDB ID(s): 5JWA, 5JWB, 5JWC

Isoelectric Point: 9.8

Protein Domain Annotations:

Source	Family ID	Description
InterPro	IPR023753	FAD/NAD(P)-binding domain
InterPro	IPR036188	FAD/NAD(P)-binding domain superfamily
PFam	PF07992	FAD/NAD(P)-binding domain
Superfamily	SSF51905	FAD/NAD(P)-binding domain superfamily

Genetic Variation

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

Homozygous genotype calls only

variant type	common	rare	doubleton	singleton
synonymous	3	24	22	40
disruptive	2	9	13	44
missense	2	9	12	36

Any inclusion in genotype call

variant type	common	rare	doubleton	singleton
synonymous	6	65	26	42
disruptive	6	42	35	117
missense	3	33	29	75

PlasmoDB Total SNPs: 59

Non-coding: 39 | Synonymous: 15 | Nonsynonymous: 5 | Stop Codon: 0

Associated Publications

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
16641458	Functional characterization and target validation of alternative complex I ofPlasmodium falciparum mitochondria.	Biagini GA, Viriyavejakul P, ..., Ward SA	10.1128/AAC.50.5.1841-1851.2006
30964863	Mitochondrial type II NADH dehydrogenase of Plasmodium falciparum (PfNDH2) isdispensable in the asexual blood stages.	Ke H, Ganesan SM, ..., Vaidya AB	10.1371/journal.pone.0214023
34494883	A Prioritized and Validated Resource of Mitochondrial Proteins in PlasmodiumIdentifies Unique Biology.	van Esveld SL, Meerstein-Kessel L, ..., Huynen MA	10.1128/mSphere.00614-21
37236355	Structure of complex III with bound antimalarial agent CK-2-68 provides insightsinto selective inhibition of Plasmodium cytochrome bc(1) complexes	Esser L, Zhou F, ..., Xia D	10.1016/j.jbc.2023.104860
38360260	The mitochondrial respiratory chain from Rhodotorula mucilaginosa, anextremophile yeast	Castaneda-Tamez P, Chiquete-Felix N, Uribe-Carvajal S, Cabrera-Orefice A	10.1016/j.bbabio.2024.149035