Genome location: Pf3D7_13_v3:1,036,517..1,039,173(-)
Genome classification: Core
Product Description: dihydrofolate synthase/folylpolyglutamate synthase
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 6.3.2.12 (Dihydrofolate synthase);6.3.2.17 (Tetrahydrofolate synthase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005737 | cytoplasm |
| Component | GO:0005829 | cytosol |
| Component | GO:0005739 | mitochondrion |
| Function | GO:0005524 | ATP binding |
| Function | GO:0008841 | dihydrofolate synthase activity |
| Function | GO:0004326 | tetrahydrofolylpolyglutamate synthase activity |
| Process | GO:0009396 | folic acid-containing compound 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 | expressed | 0.14 | 0.93 |
| Trophozoite | expressed | 0.72 | 0.60 |
| Schizont | expressed | 0.24 | 0.85 |
| Gametocyte | expressed | 0.18 | 0.89 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1324800
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: 0.123 | MFS: -3.03 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1340000)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IE69
"Best" AlphaFill ligand hit: ADP (adenosine-5'-diphosphate, Local RMSD=0.26) with 3N2A (Global RMSD=2.65)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 6.3.2.12 | dihydrofolate synthase | ADPPCMBpABA7,8-dihydrofolatedihydrofolic acidDihydroisopteroic acidTetrahydrohomopteroatedihydrohomopteroic acidp-hydroxymercuribenzoateDihydro-10-thiofolic acidDihydrofolate derivativesDihydropterin-sulfonamides... |
| 6.3.2.17 | tetrahydrofolate synthase | ADPAMPNH4+ATP4-Boratephosphate(NH4)2SO4pemetrexeddiphosphateaminopterinmethotrexatetrimethoprim... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q05932 | Folylpolyglutamate synthase, mitochondrial | Homo sapiens | OrthoDB | CHEMBL288142CHEMBL41743CHEMBL289923CHEMBL130518... |
| P48760 | Folylpolyglutamate synthase, mitochondrial | Mus musculus | OrthoDB | CHEMBL89641CHEMBL316019CHEMBL23977CHEMBL28049... |
| P08192 | Dihydrofolate synthase/folylpolyglutamate synthase | OrthoMCL | Dihydrofolic acid |
Ortholog Group (OrthoMCL): OG6_100496
Most Similar Human Ortholog: Q5JU20
TM-align score: 0.74 | RMSD: 2.13
Seq Identity: 0.33 | Length: 213 / 522
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000136877 | folylpolyglutamate synthase |
Protein Length: 522 | Molecular Weight (kDa): 60.064
PDB ID(s): None
Isoelectric Point: 6.68
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001645 | Folylpolyglutamate synthetase |
| InterPro | IPR013221 | Mur ligase, central |
| InterPro | IPR018109 | Folylpolyglutamate synthetase, conserved site |
| InterPro | IPR036565 | Mur-like, catalytic domain superfamily |
| InterPro | IPR036615 | Mur ligase, C-terminal domain superfamily |
| PFam | PF08245 | Mur ligase, central |
| Superfamily | SSF53244 | Mur ligase, C-terminal domain superfamily |
| Superfamily | SSF53623 | Mur-like, catalytic domain superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 6 | 34 | 17 | 38 |
| disruptive | 6 | 39 | 21 | 48 |
| missense | 4 | 37 | 21 | 42 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 7 | 66 | 27 | 39 |
| disruptive | 10 | 93 | 41 | 108 |
| missense | 7 | 73 | 34 | 79 |
PlasmoDB Total SNPs: 126
Non-coding: 98 | Synonymous: 23 | Nonsynonymous: 5 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 11223131 | A bifunctional dihydrofolate synthetase--folylpolyglutamate synthetase inPlasmodium falciparum identified by functional complementation in yeast andbacteria. | Salcedo E, Cortese JF, ..., Hyde JE | 10.1016/s0166-6851(00)00370-4 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 11197757 | Characterization of three genes encoding enzymes of the folate biosynthetic pathway in Plasmodium falciparum | Lee CS, Salcedo E, ..., Hyde JE | 10.1017/s0031182000006946 |