Product Description: 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (ferredoxin)
SignalP Peptide: MSYIKRLILFMLLFYSHVKI
# Transmembrane Domains: 0
EC Numbers: 1.17.7.1 ((E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase (ferredoxin));1.17.7.3 ((E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase (flavodoxin))
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Function | GO:0051539 | 4 iron, 4 sulfur cluster binding |
| Function | GO:0046429 | 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase activity |
| Function | GO:0005515 | protein binding |
| Process | GO:0019288 | isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | not expressed | N/A | N/A |
| Ring | not expressed | 0.06 | 0.97 |
| Trophozoite | possibly expressed | 0.60 | 0.66 |
| Schizont | expressed | 0.41 | 0.75 |
| Gametocyte | not expressed | 0.24 | 0.86 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1022800
Resistome Missense Mutations: L603F
Resistome Compounds with Missense Mutations: Desoxyepothilone B
Resistome # Samples with Disruptive Mutations: 1 (1 missense, 1 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.133 | MFS: -3.19 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_0507000)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IJH7
"Best" AlphaFill ligand hit: CDI (2c-methyl-d-erythritol 2,4-cyclodiphosphate, Local RMSD=0.58) with 4G9P (Global RMSD=4.21)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 1.17.7.1 | (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase (ferredoxin) | No BRENDA inhibitors |
| 1.17.7.3 | (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase (flavodoxin) | EDTAaminosulfonylcarbamateN-acyl-N'-oxysulfamatebut-3-yn-1-yl trihydrogen diphosphateprop-2-yn-1-yl trihydrogen diphosphate(2Z)-4-amino-3-methylbut-2-en-1-yl trihydrogen diphosphate(2Z)-3-methyl-4-sulfanylbut-2-en-1-yl trihydrogen diphosphate |
No evidence of orthology to BindingDB entries
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 5 | 17 | 13 | 29 |
| disruptive | 16 | 36 | 42 | 98 |
| missense | 8 | 33 | 39 | 84 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 6 | 41 | 18 | 60 |
| disruptive | 26 | 129 | 67 | 186 |
| missense | 12 | 98 | 56 | 128 |
PlasmoDB Total SNPs: 74
Non-coding: 41 | Synonymous: 14 | Nonsynonymous: 19 | Stop Codon: 0
Protein Length: 824 | Molecular Weight (kDa): 95.226
PDB ID(s): None
Isoelectric Point: 9.09
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR004588 | 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, bacterial-type |
| InterPro | IPR017178 | 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, atypical |
| PFam | PF04551 | 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, bacterial-type |
| Superfamily | SSF56014 | N/A |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 25204654 | Kinase-associated endopeptidase 1 (Kae1) participates in an atypicalribosome-associated complex in the apicoplast of Plasmodium falciparum. | Mallari JP, Oksman A, Vaupel B, Goldberg DE | 10.1074/jbc.M114.586735 |
| 28007455 | Characterization of 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (IspG)from Plasmodium vivax and it's potential as an antimalarial drug target. | Saggu GS, Garg S, ..., Saxena V | 10.1016/j.ijbiomac.2016.12.033 |
| 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 |
| 35272619 | De novo assembly and analysis of Polygonatum cyrtonema Hua and identification ofgenes involved in polysaccharide and saponin biosynthesis | Li D, Wang Q, ..., Wang H | 10.1186/s12864-022-08421-y |
| 35463632 | Apicoplast Journey and Its Essentiality as a Compartment for Malaria ParasiteSurvival | Saggu GS | 10.3389/fcimb.2022.881825 |
| 35164549 | Roles of Ferredoxin-Dependent Proteins in the Apicoplast of Plasmodium falciparumParasites | Swift RP, Rajaram K, ..., Prigge ST | 10.1128/mbio.03023-21 |