Product Description: 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase
SignalP Peptide: MFLKGYTSNVVLIILTFFILLTKE
# Transmembrane Domains: 1
EC Numbers: 4.6.1.12 (2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Function | GO:0008685 | 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase activity |
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 | possibly expressed | 0.10 | 0.95 |
| Trophozoite | expressed | 0.54 | 0.68 |
| Schizont | expressed | 0.09 | 0.94 |
| Gametocyte | not expressed | 0.40 | 0.77 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0209300
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: 0.135 | MFS: -2.98 | #Insertions: 0
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: P62368
"Best" AlphaFill ligand hit: SFY (4-amino-n-(pyridin-2-yl)benzenesulfonamide, Local RMSD=0.04) with 6MWF (Global RMSD=2.45)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 4.6.1.12 | 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase | EDTACidofovirartesunateChloroquine5-fluorocytidineCytosine arabinoside monophosphate2-amino-N-hydroxy-3-(1-H-indol-3-yl)-propionimidic acid4-amino-1-(3-O-phosphono-a-D-lyxofuranosyl)pyrimidin-2(1H)-oneN-([4-[(4-amino-2-oxopyrimidin-1(2H)-yl)methyl]-1-naphthyl]methyl)benzamideN-[4-[(6-aminopyridin-3-yl)amino]-3-methylbenzyl]-4-(trifluoromethyl)benzamideN-([4-[(4-amino-2-oxopyrimidin-1(2H)-yl)methyl]-1-naphthyl]methyl)-4-chlorobenzamide(+/-)-benzyl 6-methyl-4-(2-thienyl)-2-thioxo-1,2,3,4-tetra-hydropyrimidine-5-carboxylate... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q9CAK8 | 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, chloroplastic | OMA, OrthoDB, OrthoMCL, OrthoMCL BLAST | CHEMBL2289486 |
Protein Length: 240 | Molecular Weight (kDa): 27.161
UniProt ID(s): A0A143ZWM3, P62368
Isoelectric Point: 9.97
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR003526 | 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase |
| InterPro | IPR020555 | 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, conserved site |
| InterPro | IPR036571 | 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase superfamily |
| PFam | PF02542 | 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase |
| Superfamily | SSF69765 | 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 4 | 5 | 8 | 16 |
| disruptive | 1 | 18 | 14 | 24 |
| missense | 1 | 18 | 14 | 21 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 5 | 18 | 10 | 21 |
| disruptive | 6 | 45 | 22 | 51 |
| missense | 4 | 38 | 18 | 33 |
PlasmoDB Total SNPs: 52
Non-coding: 44 | Synonymous: 6 | Nonsynonymous: 2 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 9804551 | Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Tettelin H, ..., Hoffman SL | 10.1126/science.282.5391.1126 |
| 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 |
| 24410837 | Crystal structures of IspF from Plasmodium falciparum and Burkholderiacenocepacia: comparisons inform antimicrobial drug target assessment. | O'Rourke PE, Kalinowska-Tluscik J, ..., Hunter WN | 10.1186/1472-6807-14-1 |
| 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 |