Genome location: Pf3D7_11_v3:1,104,154..1,107,028(-)
Genome classification: Core
Product Description: bifunctional farnesyl/geranylgeranyl diphosphate synthase
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 2.5.1.1 (Dimethylallyltranstransferase);2.5.1.10 ((2E,6E)-farnesyl diphosphate synthase);2.5.1.29 (Geranylgeranyl diphosphate synthase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005737 | cytoplasm |
| Function | GO:0004161 | dimethylallyltranstransferase activity |
| Function | GO:0004311 | farnesyltranstransferase activity |
| Function | GO:0004337 | geranyltranstransferase activity |
| Process | GO:0045337 | farnesyl diphosphate biosynthetic process |
| Process | GO:0008299 | isoprenoid biosynthetic process |
| Process | GO:0009410 | response to xenobiotic stimulus |
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 | 0.05 | 0.97 |
| Trophozoite | expressed | 0.29 | 0.82 |
| Schizont | expressed | 0.04 | 0.97 |
| Gametocyte | expressed | 0.16 | 0.90 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1128400
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: 0.142 | MFS: -2.868 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_0919800)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8II79
"Best" AlphaFill ligand hit: PGO (s-1,2-propanediol, Local RMSD=0.06) with 2EWG (Global RMSD=3.51)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 2.5.1.1 | dimethylallyltranstransferase | BRENDA SOAP query unsuccessful |
| 2.5.1.10 | (2E,6E)-farnesyl diphosphate synthase | APHBPYS04070YS05035taxodoneJDS05119JDS05120celastroltaxodionearenaroneMMV019313bacitracinclodronate... |
| 2.5.1.29 | geranylgeranyl diphosphate synthase | BRENDA SOAP query unsuccessful |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q4QBL1 | Farnesyl pyrophosphate synthase | Leishmania major | HOGENOM, OMA | CHEMBL55140Bisphosphonate 1bisphosphonate, 65Bisphosphonate 3... |
| P14324 | Farnesyl pyrophosphate synthase | Homo sapiens | HOGENOM, OMA, OrthoDB | CID46398844CID46398841CID46398845CID46398840... |
| Q5CR09 | Putative farnesyl pyrophosphate synthase | Cryptosporidium parvum | OMA, OrthoDB, OrthoMCL BLAST | IBANBisphosphonate 1Bisphosphonate 3 |
| P05369 | Farnesyl pyrophosphate synthase | OrthoDB | Alendronate Sodium | |
| Q0GKD7 | Polyprenyl synthetase family protein | Plasmodium falciparum (isolate 3D7) | OrthoMCL | CHEMBL52251CHEMBL55464CHEMBL56254CHEMBL299988... |
| Q197X6 | Farnesyl diphosphate synthase | Toxoplasma gondii | OrthoMCL BLAST | CHEMBL1765146CHEMBL1765147CHEMBL1765148BPH-735... |
Ortholog Group (OrthoMCL): OG6_101661
Most Similar Human Ortholog: A0A087X090
TM-align score: 0.96 | RMSD: 1.34
Seq Identity: 0.33 | Length: 246 / 376
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000160752 | farnesyl diphosphate synthase |
Protein Length: 376 | Molecular Weight (kDa): 44.462
PDB ID(s): None
Isoelectric Point: 5.18
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000092 | Polyprenyl synthetase |
| InterPro | IPR008949 | Isoprenoid synthase domain superfamily |
| InterPro | IPR033749 | Polyprenyl synthetase, conserved site |
| InterPro | IPR039702 | Farnesyl pyrophosphate synthase-like |
| PFam | PF00348 | Polyprenyl synthetase |
| Superfamily | SSF48576 | Isoprenoid synthase domain superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 3 | 16 | 12 | 28 |
| disruptive | 5 | 17 | 10 | 26 |
| missense | 5 | 17 | 10 | 24 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 4 | 38 | 18 | 26 |
| disruptive | 11 | 45 | 23 | 66 |
| missense | 9 | 41 | 17 | 49 |
PlasmoDB Total SNPs: 200
Non-coding: 179 | Synonymous: 20 | Nonsynonymous: 1 | 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 |
| 23734739 | Cloning and characterization of bifunctional enzyme farnesyldiphosphate/geranylgeranyl diphosphate synthase from Plasmodium falciparum. | Jordao FM, Gabriel HB, ..., Katzin AM | 10.1186/1475-2875-12-184 |
| 29276048 | Specific Inhibition of the Bifunctional Farnesyl/Geranylgeranyl DiphosphateSynthase in Malaria Parasites via a New Small-Molecule Binding Site. | Gisselberg JE, Herrera Z, ..., Yeh E | https://pubmed.ncbi.nlm.nih.gov/29276048/ |
| 30110072 | Plasmodium falciparum parasites overexpressing farnesyl diphosphatesynthase/geranylgeranyl diphosphate synthase are more resistant to risedronate. | Gabriel HB, Azevedo MF, Kimura EA, Katzin AM | 10.1590/0074-02760180174 |
| 33766764 | Nonbisphosphonate inhibitors of Plasmodium falciparum FPPS/GGPPS | Kabeche S, Aida J, ..., Yeh E | 10.1016/j.bmcl.2021.127978 |
| 26688062 | Single-target high-throughput transcription analyses reveal high levels ofalternative splicing present in the FPPS/GGPPS from Plasmodium falciparum | Gabriel HB, de Azevedo MF, ..., Alves JM | 10.1038/srep18429 |