Genome location: Pf3D7_12_v3:1,332,463..1,334,896(+)
Genome classification: Core
Product Description: dihydrolipoyl dehydrogenase, mitochondrial
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 1.8.1.4 (Dihydrolipoyl dehydrogenase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0017086 | 3-methyl-2-oxobutanoate dehydrogenase (lipoamide) complex |
| Component | GO:0005759 | mitochondrial matrix |
| Component | GO:0005739 | mitochondrion |
| Component | GO:0005634 | nucleus |
| Component | GO:0045252 | oxoglutarate dehydrogenase complex |
| Function | GO:0003824 | catalytic activity |
| Function | GO:0004148 | dihydrolipoyl dehydrogenase activity |
| Function | GO:0050660 | flavin adenine dinucleotide binding |
| Function | GO:0042803 | protein homodimerization activity |
| Process | GO:0006085 | acetyl-CoA biosynthetic process |
| Process | GO:0055114 | oxidation-reduction process |
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 | 0.05 | 0.98 |
| Trophozoite | possibly expressed | 0.42 | 0.75 |
| Schizont | expressed | 0.41 | 0.74 |
| Gametocyte | expressed | 0.89 | 0.54 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1232200
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.2 | MFS: -2.776 | #Insertions: 0
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1446900)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1446900)
Modification: Disrupted | RMgm-4614
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I5A0
"Best" AlphaFill ligand hit: GSH (glutathione, Local RMSD=0.03) with 1GRA (Global RMSD=4.27)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 1.8.1.4 | dihydrolipoyl dehydrogenase | FADNAD+NADHPCMBNAD(P)+cyanidearseniteLipoamidepromazinefolic acidthioridazinePromethazine... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P9WHH9 | Dihydrolipoyl dehydrogenase | OMA, OrthoMCL | US9073941, 500US9073941, 501US9073941, 502US9073941, 503... | |
| P00390 | Glutathione reductase, mitochondrial | OrthoDB | KETOTIFENMeloxicam sodiumUS11028067, Example 2US11161815, Example 6... | |
| P61076 | Thioredoxin reductase | Plasmodium falciparum (isolate 3D7) | OrthoDB | CHEMBL383084CHEMBL383084CHEMBL383084CHEMBL380953... |
| Q16881 | Thioredoxin reductase 1, cytoplasmic | OrthoDB | US9018255, 3aUS9018255, L-3aUS9018255, D-3aUS9018255, 3b... | |
| O15770 | Glutathione reductase | Plasmodium falciparum (isolate 3D7) | OrthoDB | CHEMBL135287CHEMBL135287methylthioninium chloride |
| P41921 | Glutathione reductase | Saccharomyces cerevisiae | OrthoDB | hypericum redPseudohypericin |
| Q86VQ6 | Thioredoxin reductase 3 | OrthoDB | CHEMBL32856CHEMBL3814977CHEMBL89232CHEMBL89366... | |
| Q9Z0J5 | Thioredoxin reductase 2, mitochondrial | Rattus norvegicus | OrthoDB | PseudohypericinPseudohypericin |
| A4HSF7 | Trypanothione reductase | OrthoDB | CHEMBL242165CHEMBL4105040CHEMBL4080816CHEMBL4076896... | |
| Q962Y6 | Thioredoxin glutathione reductase | Schistosoma mansoni | OrthoDB | CHEMBL3322356CHEMBL3322293CHEMBL3322292CHEMBL3322288... |
Ortholog Group (OrthoMCL): OG6_100523
Most Similar Human Ortholog: P09622
TM-align score: 0.90 | RMSD: 1.29
Seq Identity: 0.39 | Length: 466 / 512
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000091140 | dihydrolipoamide dehydrogenase |
Protein Length: 512 | Molecular Weight (kDa): 57.228
UniProt ID(s): Q6KCB6, Q8I5A0, Q968W4
PDB ID(s): None
Isoelectric Point: 8.39
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001100 | Pyridine nucleotide-disulphide oxidoreductase, class I |
| InterPro | IPR004099 | Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain |
| InterPro | IPR006258 | Dihydrolipoamide dehydrogenase |
| InterPro | IPR012999 | Pyridine nucleotide-disulphide oxidoreductase, class I, active site |
| InterPro | IPR016156 | FAD/NAD-linked reductase, dimerisation domain superfamily |
| InterPro | IPR023753 | FAD/NAD(P)-binding domain |
| InterPro | IPR036188 | FAD/NAD(P)-binding domain superfamily |
| PFam | PF02852 | Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain |
| PFam | PF07992 | FAD/NAD(P)-binding domain |
| Superfamily | SSF51905 | FAD/NAD(P)-binding domain superfamily |
| Superfamily | SSF55424 | FAD/NAD-linked reductase, dimerisation domain superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 5 | 27 | 10 | 31 |
| disruptive | 0 | 9 | 9 | 25 |
| missense | 0 | 9 | 9 | 19 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 7 | 53 | 20 | 34 |
| disruptive | 3 | 29 | 30 | 63 |
| missense | 0 | 23 | 23 | 44 |
PlasmoDB Total SNPs: 75
Non-coding: 60 | Synonymous: 15 | Nonsynonymous: 0 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 15612914 | The human malaria parasite Plasmodium falciparum possesses two distinctdihydrolipoamide dehydrogenases. | McMillan PJ, Stimmler LM, ..., Muller S | 10.1111/j.1365-2958.2004.04398.x |
| 28836704 | A novel lipoate attachment enzyme is shared by Plasmodium and Chlamydia species. | Afanador GA, Guerra AJ, ..., Prigge ST | 10.1111/mmi.13776 |
| 30379851 | Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. | Briquet S, Ourimi A, ..., Vaquero C | 10.1371/journal.pone.0205596 |
| 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 |
| 17110466 | Dihydrolipoyl dehydrogenase as a source of reactive oxygen species inhibited bycaloric restriction and involved in Saccharomyces cerevisiae aging | Tahara EB, Barros MH, ..., Kowaltowski AJ | 10.1096/fj.06-6686com |
| 24305546 | Increased isobutanol production in Saccharomyces cerevisiae by eliminatingcompeting pathways and resolving cofactor imbalance | Matsuda F, Ishii J, ..., Kondo A | 10.1186/1475-2859-12-119 |
| 9341119 | A 13C nuclear magnetic resonance investigation of the metabolism of leucine toisoamyl alcohol in Saccharomyces cerevisiae | Dickinson JR, Lanterman MM, ..., Hewlins MJ | 10.1074/jbc.272.43.26871 |
| 10753893 | An investigation of the metabolism of isoleucine to active Amyl alcohol inSaccharomyces cerevisiae | Dickinson JR, Harrison SJ, Dickinson JA, Hewlins MJ | 10.1074/jbc.275.15.10937 |
| 29121591 | Proteomic and enzymatic response under Cr(VI) overload in yeast isolated fromtextile-dye industry effluent | Irazusta V, Bernal AR, Estevez MC, de Figueroa LIC | 10.1016/j.ecoenv.2017.10.076 |
| 9748245 | An investigation of the metabolism of valine to isobutyl alcohol in Saccharomycescerevisiae | Dickinson JR, Harrison SJ, Hewlins MJ | 10.1074/jbc.273.40.25751 |
| 28357336 | Mitochondrial proteomics of the acetic acid - induced programmed cell deathresponse in a highly tolerant Zygosaccharomyces bailii - derived hybrid strain | Guerreiro JF, Sampaio-Marques B, ..., Sa-Correia I | 10.15698/mic2016.02.477 |