About Gene List

PF3D7_1430700 (GDH2)

Genome location: Pf3D7_14_v3:1,210,949..1,213,299(+)

Genome classification: Core

Function and Localization

Product Description: NADP-specific glutamate dehydrogenase

SignalP Peptide: MILYSCVVCFIVFVFHVKAYS

# Transmembrane Domains: 0

EC Numbers: 1.4.1.4 (Glutamate dehydrogenase (NADP(+)))

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0020011 apicoplast
Component GO:0009986 cell surface
Component GO:0005829 cytosol
Function GO:0004354 glutamate dehydrogenase (NADP+) activity
Process GO:0006520 cellular amino acid metabolic process
Process GO:0006537 glutamate 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 possibly expressed 0.02 0.99
Trophozoite expressed 0.15 0.90
Schizont expressed 0.02 0.98
Gametocyte expressed 0.05 0.97

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1430700

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: 0.125 | MFS: -2.934 | #Insertions: 0

PlasmoGEM Phenotype: Insufficient data (Pb ortholog: PBANKA_1026200)

  • Relative Growth Rate: 0.50 ± 0.51
  • Confidence: 2.72

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1026200)

Modification: Disrupted | RMgm-2841

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8ILF7

"Best" AlphaFill ligand hit: ADP (adenosine-5'-diphosphate, Local RMSD=0.30) with 6DHK (Global RMSD=2.59)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
1.4.1.4 glutamate dehydrogenase (NADP+) O2ATPADPAMPKClNAD+NADHEDTANH4+NADPHNADP+HgCl2...

Orthology to BindingDB Entries:

UniProt Protein Name Species Homology Source BindingDB Ligands
P49448 Glutamate dehydrogenase 2, mitochondrial OrthoDB, OrthoMCL BLAST US8604016, 1US8604016, 1US8604016, 295US8604016, 295...
P00366 Glutamate dehydrogenase 1, mitochondrial Bos taurus OrthoDB, OrthoMCL BLAST [(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl ({[(3R,4S)-5-(3-carbamoyl-1,4-dihydropyridin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphonato}oxy)phosphonateCHEMBL2364562

Orthology Information

Ortholog Group (OrthoMCL): OG6_100455

Most Similar Human Ortholog: P49448

TM-align score: 0.77 | RMSD: 2.03

Seq Identity: 0.29 | Length: 415 / 510

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000148672 glutamate dehydrogenase 1
ENSG00000182890 glutamate dehydrogenase 2
ENSG00000288118 glutamate dehydrogenase 2

Protein Information

Protein Length: 510 | Molecular Weight (kDa): 57.343

UniProt ID(s): Q8ILF7

PDB ID(s): 3R3J

Isoelectric Point: 9.2

Protein Domain Annotations:

Source Family ID Description
InterPro IPR006095 Glutamate/phenylalanine/leucine/valine dehydrogenase
InterPro IPR006096 Glutamate/phenylalanine/leucine/valine dehydrogenase, C-terminal
InterPro IPR006097 Glutamate/phenylalanine/leucine/valine dehydrogenase, dimerisation domain
InterPro IPR014362 Glutamate dehydrogenase
InterPro IPR033524 Leu/Phe/Val dehydrogenases active site
InterPro IPR033922 NAD(P) binding domain of glutamate dehydrogenase
InterPro IPR036291 NAD(P)-binding domain superfamily
PFam PF00208 Glutamate/phenylalanine/leucine/valine dehydrogenase, C-terminal
PFam PF02812 Glutamate/phenylalanine/leucine/valine dehydrogenase, dimerisation domain
Superfamily SSF51735 NAD(P)-binding domain superfamily
Superfamily SSF53223

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 4 15 13 36
disruptive 4 29 18 50
missense 4 29 18 43

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 5 45 19 41
disruptive 8 77 35 95
missense 8 70 32 69

PlasmoDB Total SNPs: 107

Non-coding: 91 | Synonymous: 11 | Nonsynonymous: 5 | Stop Codon: 0

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
22342964 Biochemical and structural characterization of Plasmodium falciparum glutamatedehydrogenase 2. Zocher K, Fritz-Wolf K, ..., Becker K 10.1016/j.molbiopara.2012.01.007
27128092 Interrogating the Plasmodium Sporozoite Surface: Identification ofSurface-Exposed Proteins and Demonstration of Glycosylation on CSP and TRAP byMass Spectrometry-Based Proteomics. Swearingen KE, Lindner SE, ..., Sinnis P 10.1371/journal.ppat.1005606
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
38254622 Structural Evolution of Primate Glutamate Dehydrogenase 2 as Revealed by InSilico Predictions and Experimentally Determined Structures Litso I, Plaitakis A, ..., Zaganas I 10.3390/biom14010022
34653675 Carbon starvation-induced synthesis of GDH2 and PEPCK is essential for thesurvival of Pichia pastoris Dey T, Rangarajan PN 10.1016/j.bbrc.2021.10.015
38178569 Diverse mechanisms control amino acid-dependent environmental alkalization byCandida albicans Silao FGS, Valeriano VD, ..., Ljungdahl PO 10.1111/mmi.15216
38154715 The chromatin remodeler Ino80 regulates yeast stress tolerance and cellmetabolism through modulating nitrogen catabolite repression Yuan B, Wang WB, ..., Zhao XQ 10.1016/j.ijbiomac.2023.129041
36098787 Rapamycin enhanced the production of 2-phenylethanol during whole-cellbioconversion by yeast Xia H, Shangguan L, ..., Chen X 10.1007/s00253-022-12169-6