PF3D7_0815900 (aLipDH)

Genome location: Pf3D7_08_v3:743,266..745,505(+)

Genome classification: Core

Function and Localization

Product Description: dihydrolipoyl dehydrogenase, apicoplast

SignalP Peptide: N/A

# Transmembrane Domains: 1

EC Numbers: 1.8.1.4 (Dihydrolipoyl dehydrogenase)

Curated GO (PlasmoDB):

Type	GO Term	Name
Component	GO:0020011	apicoplast
Function	GO:0004148	dihydrolipoyl dehydrogenase activity
Function	GO:0050660	flavin adenine dinucleotide binding
Function	GO:0042803	protein homodimerization activity
Process	GO:0006086	acetyl-CoA biosynthetic process from pyruvate
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	0.02	0.99
Trophozoite	possibly expressed	0.09	0.95
Schizont	possibly expressed	0.06	0.96
Gametocyte	expressed	0.13	0.92

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0815900

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: 0.999 | MFS: -0.134 | #Insertions: 2

PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1446900)

Relative Growth Rate: 0.83 ± 0.08
Confidence: 6.55

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_0714900)

Modification: Disrupted | RMgm-2246

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IAZ6

"Best" AlphaFill ligand hit: FAD (flavin-adenine dinucleotide, Local RMSD=0.04) with 6UZI (Global RMSD=6.49)

BRENDA EC Inhibitors:

EC #	Name	EC Inhibitors
1.8.1.4	dihydrolipoyl dehydrogenase	FADNAD+NADHPCMBNAD(P)+cyanidearseniteLipoamidepromazinefolic acidthioridazinePromethazine...

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_100523

Most Similar Human Ortholog: P09622

TM-align score: 0.89 | RMSD: 2.20

Seq Identity: 0.32 | Length: 474 / 666

All Human Orthologs (OrthoMCL):

Gene ID	Description
ENSG00000091140	dihydrolipoamide dehydrogenase

Genetic Variation

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

Homozygous genotype calls only

variant type	common	rare	doubleton	singleton
synonymous	14	21	11	44
disruptive	12	61	36	113
missense	12	60	36	109

Any inclusion in genotype call

variant type	common	rare	doubleton	singleton
synonymous	19	47	32	54
disruptive	25	167	74	182
missense	22	150	61	122

PlasmoDB Total SNPs: 47

Non-coding: 27 | Synonymous: 13 | Nonsynonymous: 7 | Stop Codon: 0

Protein Information

Protein Length: 666 | Molecular Weight (kDa): 75.587

UniProt ID(s): Q5VGY1, Q8IAZ6

PDB ID(s): None

Isoelectric Point: 9.54

Protein Domain Annotations:

Source	Family ID	Description
InterPro	IPR004099	Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain
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

PMID	Title	Authors	DOI/Link
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
25387830	Biochemical and structural characterization of the apicoplast dihydrolipoamidedehydrogenase of Plasmodium falciparum	Laine LM, Biddau M, Byron O, Muller S	10.1042/BSR20140150
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