PF3D7_0820700 (KDH)

Genome location: Pf3D7_08_v3:931,673..935,916(+)

Genome classification: Core

Function and Localization

Product Description: 2-oxoglutarate dehydrogenase E1 component

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 1.2.4.2 (Oxoglutarate dehydrogenase (succinyl-transferring))

Curated GO (PlasmoDB):

Type	GO Term	Name
Component	GO:0005759	mitochondrial matrix
Component	GO:0005739	mitochondrion
Component	GO:0045252	oxoglutarate dehydrogenase complex
Function	GO:0004591	oxoglutarate dehydrogenase (succinyl-transferring) activity
Process	GO:0006103	2-oxoglutarate metabolic process
Process	GO:0006099	tricarboxylic acid cycle

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	not expressed	0.09	0.95
Trophozoite	expressed	0.58	0.67
Schizont	expressed	0.28	0.82
Gametocyte	expressed	0.49	0.72

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0820700

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: -1.656 | #Insertions: 3

PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_0710100)

Relative Growth Rate: 0.97 ± 0.18
Confidence: 4.87

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_0710100)

Modification: Disrupted | RMgm-2215

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8I6S5

"Best" AlphaFill ligand hit: ACO (acetyl coenzyme *a, Local RMSD=0.15) with 2XTA (Global RMSD=3.53)

BRENDA EC Inhibitors:

EC #	Name	EC Inhibitors
1.2.4.2	oxoglutarate dehydrogenase (succinyl-transferring)	NAD+glutathioneruthenium redadipoyl phosphonatesuccinylphosphonatesuccinyl phosphonateglutaryl phosphonatephosphono ethyl succinyl phosphonate

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_100311

Most Similar Human Ortholog: Q96HY7

TM-align score: 0.91 | RMSD: 2.06

Seq Identity: 0.37 | Length: 857 / 1038

All Human Orthologs (OrthoMCL):

Gene ID	Description
ENSG00000105953	oxoglutarate dehydrogenase
ENSG00000181192	dehydrogenase E1 and transketolase domain containing 1
ENSG00000197444	oxoglutarate dehydrogenase L

Genetic Variation

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

Homozygous genotype calls only

variant type	common	rare	doubleton	singleton
synonymous	13	47	34	80
disruptive	9	33	32	85
missense	9	32	31	76

Any inclusion in genotype call

variant type	common	rare	doubleton	singleton
synonymous	22	129	50	62
disruptive	13	102	82	232
missense	12	87	65	150

PlasmoDB Total SNPs: 185

Non-coding: 142 | Synonymous: 31 | Nonsynonymous: 12 | Stop Codon: 0

Protein Information

Protein Length: 1038 | Molecular Weight (kDa): 121.15

UniProt ID(s): Q8I6S5

PDB ID(s): None

Isoelectric Point: 7.82

Protein Domain Annotations:

Source	Family ID	Description
InterPro	IPR001017	Dehydrogenase, E1 component
InterPro	IPR005475	Transketolase-like, pyrimidine-binding domain
InterPro	IPR011603	2-oxoglutarate dehydrogenase E1 component
InterPro	IPR029061	Thiamin diphosphate-binding fold
InterPro	IPR031717	Multifunctional 2-oxoglutarate metabolism enzyme, C-terminal
PFam	PF00676	Dehydrogenase, E1 component
PFam	PF02779	Transketolase-like, pyrimidine-binding domain
PFam	PF16870	Multifunctional 2-oxoglutarate metabolism enzyme, C-terminal
Superfamily	SSF52518	Thiamin diphosphate-binding fold

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
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