Genome location: Pf3D7_14_v3:2,209,313..2,213,595(-)
Genome classification: Core
Product Description: glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 1.1.1.49 (Glucose-6-phosphate dehydrogenase (NADP(+)));3.1.1.31 (6-phosphogluconolactonase);3.5.99.6 (Glucosamine-6-phosphate deaminase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005829 | cytosol |
| Function | GO:0017057 | 6-phosphogluconolactonase activity |
| Function | GO:0003723 | RNA binding |
| Function | GO:0004345 | glucose-6-phosphate dehydrogenase activity |
| Process | GO:0051156 | glucose 6-phosphate metabolic process |
| Process | GO:0006098 | pentose-phosphate shunt |
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 | 0.43 | 0.79 |
| Trophozoite | expressed | 0.44 | 0.74 |
| Schizont | expressed | 0.29 | 0.81 |
| Gametocyte | expressed | 0.25 | 0.85 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1453800
Resistome Missense Mutations: D152Y
Resistome Compounds with Missense Mutations: MMV030084/TCMDC-140369
Resistome # Samples with Disruptive Mutations: 1 (1 missense, 1 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.121 | MFS: -2.984 | #Insertions: 0
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1317500)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1317500)
Modification: Disrupted | RMgm-3489
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IKU0
"Best" AlphaFill ligand hit: NDP (nadph dihydro-nicotinamide-adenine-dinucleotide phosphate, Local RMSD=0.46) with 5AQ1 (Global RMSD=2.48)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 1.1.1.49 | glucose-6-phosphate dehydrogenase (NADP+) | ATPADPCoAAMPGTPDTTITPNADHEDTARNAiNADPHNADP+... |
| 3.1.1.31 | 6-phosphogluconolactonase | (NH4)2SO4glutathioneellagic acidglucose-6-phosphateguanidine hydrochloride |
| 3.5.99.6 | glucosamine-6-phosphate deaminase | EDTAPCMBcysteinephosphatediphosphatefluorescaminediethyl dicarbonateD-glucose 6-phosphateD-fructose 6-phosphateUDP-N-acetylglucosamineD-glucosamine 6-phosphateD-fructose 1,6-diphosphate... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q8IKU0 | Bifunctional glucose-6-phosphate 1-dehydrogenase/6-phosphogluconolactonase | HOGENOM, OMA, OrthoDB, OrthoMCL, OrthoMCL BLAST | CHEMBL2170943CHEMBL4165870 | |
| P11412 | Glucose-6-phosphate 1-dehydrogenase | OrthoDB, OrthoMCL | Epigallocatechin 3-gallateCHEMBL129451Epicatechin-3-O-gallateGallocatechin 3-O-gallate | |
| P11413 | Glucose-6-phosphate 1-dehydrogenase | OrthoDB | acs.jmedchem.1c00409_ST.178MLS000697055KETOTIFENDehydroepiandrosterone (1)... | |
| Q25856 | Glucose-6-phosphate dehydrogenase | Plasmodium falciparum | OrthoMCL BLAST | MLS001030711CHEMBL2170930CHEMBL2170929CHEMBL2171113... |
| Q9BHT9 | Glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase | Plasmodium falciparum (isolate 3D7) | OrthoMCL BLAST | MLS000077300MLS000031979MLS000068655MLS000033777... |
Ortholog Group (OrthoMCL): OG6_100726
Most Similar Human Ortholog: P11413
TM-align score: 0.91 | RMSD: 1.76
Seq Identity: 0.40 | Length: 487 / 910
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000160211 | glucose-6-phosphate dehydrogenase |
Protein Length: 910 | Molecular Weight (kDa): 106.987
UniProt ID(s): A0A144A6N0, Q25856, Q27741, Q8IKU0
PDB ID(s): None
Isoelectric Point: 6.83
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001282 | Glucose-6-phosphate dehydrogenase |
| InterPro | IPR006148 | Glucosamine/galactosamine-6-phosphate isomerase |
| InterPro | IPR022674 | Glucose-6-phosphate dehydrogenase, NAD-binding |
| InterPro | IPR022675 | Glucose-6-phosphate dehydrogenase, C-terminal |
| InterPro | IPR036291 | NAD(P)-binding domain superfamily |
| InterPro | IPR037171 | NagB/RpiA transferase-like |
| PFam | PF00479 | Glucose-6-phosphate dehydrogenase, NAD-binding |
| PFam | PF01182 | Glucosamine/galactosamine-6-phosphate isomerase |
| PFam | PF02781 | Glucose-6-phosphate dehydrogenase, C-terminal |
| Superfamily | SSF100950 | NagB/RpiA transferase-like |
| Superfamily | SSF51735 | NAD(P)-binding domain superfamily |
| Superfamily | SSF55347 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 7 | 49 | 25 | 74 |
| disruptive | 21 | 63 | 37 | 93 |
| missense | 20 | 60 | 30 | 79 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 13 | 104 | 39 | 63 |
| disruptive | 41 | 131 | 69 | 163 |
| missense | 34 | 109 | 58 | 102 |
PlasmoDB Total SNPs: 139
Non-coding: 85 | Synonymous: 29 | Nonsynonymous: 25 | 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 |
| 16689939 | Transient silencing of Plasmodium falciparum bifunctional glucose-6-phosphatedehydrogenase- 6-phosphogluconolactonase. | Crooke A, Diez A, Mason PJ, Bautista JM | 10.1111/j.1742-4658.2006.05174.x |
| 21443518 | Glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase: a uniquebifunctional enzyme from Plasmodium falciparum. | Jortzik E, Mailu BM, ..., Becker K | 10.1042/BJ20110170 |
| 26198663 | Plasmodium falciparum glucose-6-phosphate dehydrogenase 6-phosphogluconolactonaseis a potential drug target. | Allen SM, Lim EE, ..., Ralph SA | 10.1111/febs.13380 |
| 33906926 | Functional Characterization of the m(6)A-Dependent Translational Modulator PfYTH | Sinha A, Baumgarten S, ..., Scherf A | 10.1128/mBio.00661-21 |
| 30683097 | Glucose 6-phosphate dehydrogenase 6-phosphogluconolactonase: characterization ofthe Plasmodium vivax enzyme and inhibitor studies | Haeussler K, Berneburg I, ..., Becker K | 10.1186/s12936-019-2651-z |
| 35266827 | An Optimized Dihydrodibenzothiazepine Lead Compound (SBI-0797750) as a Potent andSelective Inhibitor of Plasmodium falciparum and P. vivax Glucose 6-PhosphateDehydrogenase 6-Phosphogluconolactonase | Berneburg I, Peddibhotla S, ..., Pinkerton AB | 10.1128/aac.02109-21 |