PF3D7_0802000 (GDH3)

Genome location: Pf3D7_08_v3:145,632..151,659(+)

Genome classification: Core

Function and Localization

Product Description: glutamate dehydrogenase, putative

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 1.4.1.2 (Glutamate dehydrogenase)

Curated GO (PlasmoDB):

Type	GO Term	Name
Component	GO:0005829	cytosol
Component	GO:0005739	mitochondrion
Component	GO:0005634	nucleus
Function	GO:0004352	glutamate dehydrogenase (NAD+) activity
Process	GO:0006538	glutamate catabolic process
Process	GO:0006536	glutamate metabolic 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	0.50	0.77
Trophozoite	expressed	1.58	0.29
Schizont	expressed	0.52	0.70
Gametocyte	expressed	0.52	0.72

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0802000

Resistome Missense Mutations: K64Q, D200Y

Resistome Compounds with Missense Mutations: MMV006901, MMV407834, OSM-S-106

Resistome # Samples with Disruptive Mutations: 16 (16 missense, 16 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Mutable in CDS

MIS: 0.956 | MFS: -2.853 | #Insertions: 1

PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_1228200)

Relative Growth Rate: 0.96 ± 0.17
Confidence: 4.93

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1228200)

Modification: Disrupted | RMgm-4271

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IAM0

"Best" AlphaFill ligand hit: NAD (nicotinamide-adenine-dinucleotide, Local RMSD=1.50) with 8OWM (Global RMSD=4.46)

BRENDA EC Inhibitors:

EC #	Name	EC Inhibitors
1.4.1.2	glutamate dehydrogenase	ATPADPAMPGTPGDPKClCMPKCNNAD+NADHEDTANH4+...

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_106160

No human ortholog(s)

Genetic Variation

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

Homozygous genotype calls only

variant type	common	rare	doubleton	singleton
synonymous	13	70	39	95
disruptive	16	63	45	122
missense	14	62	42	104

Any inclusion in genotype call

variant type	common	rare	doubleton	singleton
synonymous	24	143	68	117
disruptive	27	160	99	261
missense	21	130	79	198

PlasmoDB Total SNPs: 249

Non-coding: 207 | Synonymous: 27 | Nonsynonymous: 15 | Stop Codon: 0

Protein Information

Protein Length: 1397 | Molecular Weight (kDa): 160.425

UniProt ID(s): Q8IAM0, Q9NGT0

PDB ID(s): None

Isoelectric Point: 6.72

Protein Domain Annotations:

Source	Family ID	Description
InterPro	IPR006096	Glutamate/phenylalanine/leucine/valine dehydrogenase, C-terminal
InterPro	IPR036291	NAD(P)-binding domain superfamily
PFam	PF00208	Glutamate/phenylalanine/leucine/valine dehydrogenase, C-terminal
Superfamily	SSF51735	NAD(P)-binding domain superfamily
Superfamily	SSF53223

Associated Publications

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
22342964	Biochemical and structural characterization of Plasmodium falciparum glutamatedehydrogenase 2.	Zocher K, Fritz-Wolf K, ..., Becker K	10.1016/j.molbiopara.2012.01.007
23181666	Organellar proteomics reveals hundreds of novel nuclear proteins in the malariaparasite Plasmodium falciparum.	Oehring SC, Woodcroft BJ, ..., Voss TS	10.1186/gb-2012-13-11-r108
24490132	Ebselen induces reactive oxygen species (ROS)-mediated cytotoxicity inSaccharomyces cerevisiae with inhibition of glutamate dehydrogenase being atarget	Azad GK, Singh V, ..., Tomar RS	10.1016/j.fob.2014.01.002
23105103	Involvement of GDH3-encoded NADP+-dependent glutamate dehydrogenase in yeast cellresistance to stress-induced apoptosis in stationary phase cells	Lee YJ, Kim KJ, ..., Maeng PJ	10.1074/jbc.M112.375360
27864882	Diversification of the kinetic properties of yeast NADP-glutamate-dehydrogenaseisozymes proceeds independently of their evolutionary origin	Campero-Basaldua C, Quezada H, ..., Gonzalez A	10.1002/mbo3.419
22068328	Mapping the interaction of Snf1 with TORC1 in Saccharomyces cerevisiae	Zhang J, Vaga S, ..., Nielsen J	10.1038/msb.2011.80
31376105	The NADP(+)-dependent glutamate dehydrogenase Gdh1 is subjected to glucosestarvation-induced reversible aggregation that affects stress resistance inyeast	Lee WH, Oh JY, Maeng PJ	10.1007/s12275-019-9065-z
21242068	(1)(3)C-metabolic enrichment of glutamate in glutamate dehydrogenase mutants ofSaccharomyces cerevisiae	Tang Y, Sieg A, Trotter PJ	10.1016/j.micres.2010.10.004
30384856	The pleiotropic effects of the glutamate dehydrogenase (GDH) pathway inSaccharomyces cerevisiae	Mara P, Fragiadakis GS, Gkountromichos F, Alexandraki D	10.1186/s12934-018-1018-4