Genome location: Pf3D7_13_v3:1,795,375..1,798,284(+)
Genome classification: Core
Product Description: aspartate carbamoyltransferase
SignalP Peptide: N/A
# Transmembrane Domains: 1
EC Numbers: 2.1.3.2 (Aspartate carbamoyltransferase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005634 | nucleus |
| 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 | 0.15 | 0.93 |
| Trophozoite | expressed | 0.37 | 0.77 |
| Schizont | expressed | 0.05 | 0.97 |
| Gametocyte | expressed | 0.24 | 0.86 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1344800
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: 0.408 | MFS: -2.437 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1357700)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: A0A5K1K910
"Best" AlphaFill ligand hit: D48 (naphthalene-2,3-diol, Local RMSD=0.09) with 6FBA (Global RMSD=1.55)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 2.1.3.2 | aspartate carbamoyltransferase | ATPADPUDPGTPGDPCTPUTPUMPCDPITPdCTPYD19... |
Orthology to BindingDB Entries:
Protein Length: 375 | Molecular Weight (kDa): 43.252
UniProt ID(s): A0A5K1K910, O15804
PDB ID(s): 5ILN, 5ILQ, 7ZCZ, 7ZEA, 7ZGS, 7ZHI, 7ZID, 7ZP2, 7ZST
Isoelectric Point: 8.61
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR002082 | Aspartate carbamoyltransferase |
| InterPro | IPR006130 | Aspartate/ornithine carbamoyltransferase |
| InterPro | IPR006131 | Aspartate/ornithine carbamoyltransferase, Asp/Orn-binding domain |
| InterPro | IPR006132 | Aspartate/ornithine carbamoyltransferase, carbamoyl-P binding |
| InterPro | IPR036901 | Aspartate/ornithine carbamoyltransferase superfamily |
| PFam | PF00185 | Aspartate/ornithine carbamoyltransferase, Asp/Orn-binding domain |
| PFam | PF02729 | Aspartate/ornithine carbamoyltransferase, carbamoyl-P binding |
| Superfamily | SSF53671 | Aspartate/ornithine carbamoyltransferase superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 1 | 29 | 14 | 27 |
| disruptive | 5 | 33 | 26 | 60 |
| missense | 5 | 31 | 25 | 58 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 9 | 47 | 17 | 30 |
| disruptive | 12 | 84 | 55 | 92 |
| missense | 9 | 73 | 52 | 61 |
PlasmoDB Total SNPs: 121
Non-coding: 98 | Synonymous: 16 | Nonsynonymous: 7 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 29476738 | Identification of a non-competitive inhibitor of Plasmodium falciparum aspartatetranscarbamoylase. | Lunev S, Bosch SS, ..., Groves MR | https://pubmed.ncbi.nlm.nih.gov/29476738/ |
| 30379851 | Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. | Briquet S, Ourimi A, ..., Vaquero C | 10.1371/journal.pone.0205596 |
| 32129597 | Molecular Target Validation of Aspartate Transcarbamoylase from Plasmodiumfalciparum by Torin 2. | Bosch SS, Lunev S, ..., Wrenger C | 10.1021/acsinfecdis.9b00411 |
| 31947715 | Conformational Plasticity of the Active Site Entrance in E. coli AspartateTranscarbamoylase and Its Implication in Feedback Regulation | Lei Z, Wang N, ..., Jia Z | 10.3390/ijms21010320 |
| 24316846 | Expression, purification, crystallization and preliminary X-ray diffractionanalysis of the aspartate transcarbamoylase domain of human CAD | Ruiz-Ramos A, Lallous N, Grande-Garcia A, Ramon-Maiques S | 10.1107/S1744309113031114 |
| 37384746 | Unlocking the Secrets of Streptococcus suis: A peptidomics comparison of virulentand non-virulent serotypes 2, 14, 18, and 19 | Chaiden C, Jaresitthikunchai J, ..., Nuanualsuwan S | 10.1371/journal.pone.0287639 |
| 30657257 | Pressure-induced activation of latent dihydroorotase from Aquifex aeolicus asrevealed by high pressure protein crystallography | Prange T, Girard E, ..., Evans DR | 10.1111/febs.14758 |
| 28833948 | Charge neutralization in the active site of the catalytic trimer of aspartate transcarbamoylase promotes diverse structural changes | Endrizzi JA, Beernink PT | 10.1002/pro.3277 |
| 37294060 | Inhibitors of Aspartate Transcarbamoylase Inhibit Mycobacterium tuberculosisGrowth | Du X, Sonawane V, ..., Groves MR | 10.1002/cmdc.202300279 |
| 35644497 | Subsets of Slow Dynamic Modes Reveal Global Information Sources as AllostericSites | Altintel B, Acar B, Erman B, Haliloglu T | 10.1016/j.jmb.2022.167644 |
| 35310840 | Novel Highlight in Malarial Drug Discovery: Aspartate Transcarbamoylase | Wang C, Kruger A, ..., Groves MR | 10.3389/fcimb.2022.841833 |
| 30038211 | Allostery and cooperativity in multimeric proteins: bond-to-bond propensities inATCase | Hodges M, Barahona M, Yaliraki SN | 10.1038/s41598-018-27992-z |
| 32126100 | Characterization and assembly of the Pseudomonas aeruginosa aspartate transcarbamoylase-pseudo dihydroorotase complex | Patel C, Vaishnav A, Edwards BFP, Evans DR | 10.1371/journal.pone.0229494 |
| 27265852 | Structure and Functional Characterization of Human Aspartate Transcarbamoylase,the Target of the Anti-tumoral Drug PALA | Ruiz-Ramos A, Velazquez-Campoy A, ..., Ramon-Maiques S | 10.1016/j.str.2016.05.001 |
| 32328112 | Chemical Synthesis, Efficacy, and Safety of Antimalarial Hybrid Drug Comprisingof Sarcosine and Aniline Pharmacophores as Scaffolds | Niyibizi JB, Kirira PG, ..., Ng'ang'a JK | 10.1155/2020/1643015 |
| 24138583 | New paradigm for allosteric regulation of Escherichia coli aspartate transcarbamoylase | Cockrell GM, Zheng Y, ..., Kantrowitz ER | 10.1021/bi401205n |
| 26274952 | From Genome to Structure and Back Again: A Family Portrait of theTranscarbamylases | Shi D, Allewell NM, Tuchman M | 10.3390/ijms160818836 |
| 31967710 | New regulatory mechanism-based inhibitors of aspartate transcarbamoylase forpotential anticancer drug development | Lei Z, Wang B, ..., Jia Z | 10.1111/febs.15220 |