Genome location: Pf3D7_06_v3:1,113,448..1,117,623(-)
Genome classification: Core
Product Description: acetyl-CoA synthetase
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 6.2.1.1 (Acetate--CoA ligase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005634 | nucleus |
| Function | GO:0003987 | acetate-CoA ligase activity |
| Process | GO:0006085 | acetyl-CoA biosynthetic process |
| Process | GO:0019427 | acetyl-CoA biosynthetic process from acetate |
| Process | GO:0006325 | chromatin organization |
| Process | GO:0006091 | generation of precursor metabolites and energy |
| Process | GO:0016573 | histone acetylation |
| 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 | 0.63 | 0.69 |
| Trophozoite | expressed | 0.62 | 0.64 |
| Schizont | expressed | 0.44 | 0.72 |
| Gametocyte | possibly expressed | 0.37 | 0.79 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0627800
Resistome Missense Mutations: A597V, Y607C, T648M, A652T, A652S
Resistome Compounds with Missense Mutations: MMV019721, MMV084978
Resistome # Samples with Disruptive Mutations: 12 (12 missense, 12 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.168 | MFS: -2.84 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1126500)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: C6KTB4
"Best" AlphaFill ligand hit: COA (coenzyme a, Local RMSD=0.05) with 5JRH (Global RMSD=9.70)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 6.2.1.1 | acetate-CoA ligase | BRENDA SOAP query unsuccessful |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q9NR19 | Acetyl-coenzyme A synthetase, cytoplasmic | OMA, OrthoDB | CHEMBL4846168US20230271956, Compound 2US20230271956, Compound 3US20230271956, Compound 4... |
Ortholog Group (OrthoMCL): OG6_100430
Most Similar Human Ortholog: C9J7L5
TM-align score: 0.91 | RMSD: 1.14
Seq Identity: 0.43 | Length: 156 / 997
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000131069 | acyl-CoA synthetase short chain family member 2 |
| ENSG00000154930 | acyl-CoA synthetase short chain family member 1 |
Protein Length: 997 | Molecular Weight (kDa): 113.881
UniProt ID(s): C6KTB4
PDB ID(s): None
Isoelectric Point: 7.82
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000873 | AMP-dependent synthetase/ligase |
| InterPro | IPR020845 | AMP-binding, conserved site |
| InterPro | IPR025110 | AMP-binding enzyme, C-terminal domain |
| InterPro | IPR032387 | Acetyl-coenzyme A synthetase, N-terminal domain |
| PFam | PF00501 | AMP-dependent synthetase/ligase |
| PFam | PF13193 | AMP-binding enzyme, C-terminal domain |
| PFam | PF16177 | Acetyl-coenzyme A synthetase, N-terminal domain |
| Superfamily | SSF56801 | N/A |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 16 | 16 | 5 | 31 |
| disruptive | 35 | 43 | 24 | 81 |
| missense | 32 | 38 | 21 | 65 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 18 | 36 | 17 | 43 |
| disruptive | 52 | 108 | 66 | 175 |
| missense | 42 | 79 | 55 | 110 |
PlasmoDB Total SNPs: 169
Non-coding: 120 | Synonymous: 22 | Nonsynonymous: 27 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368867 | Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | Hall N, Pain A, ..., Barrell BG | 10.1038/nature01095 |
| 23181666 | Organellar proteomics reveals hundreds of novel nuclear proteins in the malariaparasite Plasmodium falciparum. | Oehring SC, Woodcroft BJ, ..., Voss TS | 10.1186/gb-2012-13-11-r108 |
| 34348113 | Chemogenomics identifies acetyl-coenzyme A synthetase as a target for malariatreatment and prevention. | Summers RL, Pasaje CFA, ..., Lukens AK | 10.1016/j.chembiol.2021.07.010 |
| 34766750 | Plasmodium falciparum Acetyl-CoA Synthetase Is Essential for ParasiteIntraerythrocytic Development and Chromatin Modification. | Prata IO, Cubillos EFG, ..., Wunderlich G | 10.1021/acsinfecdis.1c00414 |