About Gene List

PF3D7_1124500 (pdhA)

Genome location: Pf3D7_11_v3:966,719..969,467(+)

Genome classification: Core

Function and Localization

Product Description: pyruvate dehydrogenase E1 component subunit alpha

SignalP Peptide: N/A

# Transmembrane Domains: 2

EC Numbers: 1.2.4.1 (Pyruvate dehydrogenase (acetyl-transferring))

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0020011 apicoplast
Component GO:0045254 pyruvate dehydrogenase complex
Function GO:0004739 pyruvate dehydrogenase (acetyl-transferring) activity
Process GO:0006086 acetyl-CoA biosynthetic process from pyruvate
Process GO:0006633 fatty acid biosynthetic process

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 0.05 0.97
Trophozoite expressed 0.13 0.92
Schizont expressed 0.04 0.97
Gametocyte expressed 0.50 0.71

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1124500

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: Non - Mutable in CDS

MIS: 0.492 | MFS: -2.286 | #Insertions: 0

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_0923800)

  • Relative Growth Rate: 0.04 ± 0.06
  • Confidence: 7.06

RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PBANKA_0923800)

Modification: Disrupted | RMgm-854

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IIB8

"Best" AlphaFill ligand hit: PYR (pyruvic acid, Local RMSD=0.06) with 3DV0 (Global RMSD=5.14)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
1.2.4.1 pyruvate dehydrogenase (acetyl-transferring) BRENDA SOAP query unsuccessful

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_100754

Most Similar Human Ortholog: P08559

TM-align score: 0.82 | RMSD: 2.85

Seq Identity: 0.30 | Length: 350 / 608

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000131828 pyruvate dehydrogenase E1 subunit alpha 1
ENSG00000163114 pyruvate dehydrogenase E1 subunit alpha 2

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 6 22 11 39
disruptive 10 54 28 74
missense 10 52 28 64

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 8 47 26 43
disruptive 25 127 50 178
missense 19 115 42 116

PlasmoDB Total SNPs: 119

Non-coding: 64 | Synonymous: 42 | Nonsynonymous: 13 | Stop Codon: 0

Protein Information

Protein Length: 608 | Molecular Weight (kDa): 70.847

UniProt ID(s): Q5VGY4, Q8IIB8

PDB ID(s): None

Isoelectric Point: 8.28

Protein Domain Annotations:

Source Family ID Description
InterPro IPR001017 Dehydrogenase, E1 component
InterPro IPR029061 Thiamin diphosphate-binding fold
PFam PF00676 Dehydrogenase, E1 component
Superfamily SSF52518 Thiamin diphosphate-binding fold

Associated Publications

PMID Title Authors DOI/Link
12368864 Genome sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Hall N, ..., Barrell B 10.1038/nature01097
15612915 The malaria parasite Plasmodium falciparum has only one pyruvate dehydrogenasecomplex, which is located in the apicoplast. Foth BJ, Stimmler LM, ..., McFadden GI 10.1111/j.1365-2958.2004.04407.x
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
32341123 Acquisition of exogenous fatty acids renders apicoplast-based biosynthesisdispensable in tachyzoites of Toxoplasma. Liang X, Cui J, ..., Shen B 10.1074/jbc.RA120.013004