Genome location: Pf3D7_13_v3:1,885,939..1,888,476(+)
Genome classification: Core
Product Description: DNA topoisomerase 3
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 5.6.2.1 (DNA topoisomerase);5.99.1.2 (Transferred entry: 5.6.2.1)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005739 | mitochondrion |
| Component | GO:0005634 | nucleus |
| Function | GO:0003677 | DNA binding |
| Function | GO:0003916 | DNA topoisomerase activity |
| Function | GO:0005515 | protein binding |
| Process | GO:0006265 | DNA topological change |
| Process | GO:0006268 | DNA unwinding involved in DNA replication |
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 | 0.11 | 0.94 |
| Trophozoite | expressed | 0.60 | 0.66 |
| Schizont | expressed | 0.39 | 0.76 |
| Gametocyte | expressed | 0.65 | 0.64 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1347100
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 1 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.391 | MFS: -2.648 | #Insertions: 0
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1360000)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1360000)
Modification: Disrupted | RMgm-3698
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IDM7
"Best" AlphaFill ligand hit: COH (protoporphyrin ix containing co, Local RMSD=2.58) with 5F19 (Global RMSD=21.61)
BRENDA EC Inhibitors:
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P96583 | DNA topoisomerase 3 | Bacillus subtilis | OMA | CHEMBL293964CHEMBL52034CHEMBL54782CHEMBL54950... |
Ortholog Group (OrthoMCL): OG6_101027
Most Similar Human Ortholog: Q13472
TM-align score: 0.84 | RMSD: 1.47
Seq Identity: 0.40 | Length: 606 / 710
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000177302 | DNA topoisomerase III alpha |
| ENSG00000284238 | DNA topoisomerase III alpha |
Protein Length: 710 | Molecular Weight (kDa): 84.306
UniProt ID(s): Q8IDM7
PDB ID(s): None
Isoelectric Point: 9.26
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000380 | DNA topoisomerase, type IA |
| InterPro | IPR003601 | DNA topoisomerase, type IA, domain 2 |
| InterPro | IPR003602 | DNA topoisomerase, type IA, DNA-binding domain |
| InterPro | IPR006171 | TOPRIM domain |
| InterPro | IPR013497 | DNA topoisomerase, type IA, central |
| InterPro | IPR023405 | DNA topoisomerase, type IA, core domain |
| InterPro | IPR034144 | DNA topoisomerase 3-like, TOPRIM domain |
| PFam | PF01131 | DNA topoisomerase, type IA, central |
| PFam | PF01751 | TOPRIM domain |
| Superfamily | SSF56712 | DNA topoisomerase, type IA, core domain |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 4 | 25 | 10 | 43 |
| disruptive | 9 | 42 | 30 | 75 |
| missense | 8 | 39 | 27 | 63 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 9 | 63 | 22 | 42 |
| disruptive | 36 | 118 | 71 | 124 |
| missense | 20 | 81 | 51 | 74 |
PlasmoDB Total SNPs: 66
Non-coding: 11 | Synonymous: 39 | Nonsynonymous: 13 | Stop Codon: 3
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 33241842 | Elucidation of an essential function of the unique charged domain of Plasmodiumtopoisomerase I II | Bansod S, Bung N, ..., Bhattacharyya S | 10.1042/BCJ20200318 |
| 34494883 | A Prioritized and Validated Resource of Mitochondrial Proteins in PlasmodiumIdentifies Unique Biology. | van Esveld SL, Meerstein-Kessel L, ..., Huynen MA | 10.1128/mSphere.00614-21 |
| 34730376 | Bloom Helicase Along with Recombinase Rad51 Repairs the Mitochondrial Genome ofthe Malaria Parasite. | Jha P, Gahlawat A, ..., Bhattacharyya MK | 10.1128/mSphere.00718-21 |
| 38203410 | Molecular Dynamics Investigations of Human DNA-Topoisomerase I Interacting withNovel Dewar Valence Photo-Adducts: Insights into Inhibitory Activity | Di Martino J, Arcieri M, ..., Saladino R | 10.3390/ijms25010234 |
| 38185054 | Camptothecin structure simplification elaborated new imidazo[2,1-b]quinazolinederivative as a human topoisomerase I inhibitor with efficacy against bone cancercells and colon adenocarcinoma | Khodair AI, El-Hallouty SM, ..., Kassab SE | 10.1016/j.ejmech.2023.116049 |
| 38086241 | Design and synthesis of luotonin A-derived topoisomerase targeting scaffold with potent antitumor effect and low genotoxicity | Li XW, Fang SJ, ..., Pan CX | 10.1016/j.bioorg.2023.107015 |
| 38315739 | Nonhomologous tails direct heteroduplex rejection and mismatch correction duringsingle-strand annealing in Saccharomyces cerevisiae | Sapede E, Sugawara N, ..., Haber JE | 10.1371/journal.pgen.1010527 |
| 38007027 | DNA topoisomerases as a drug target in Leishmaniasis: Structural and mechanisticinsights | Kour P, Saha P, Sharma DK, Singh K | 10.1016/j.ijbiomac.2023.128401 |