Genome location: Pf3D7_12_v3:1,648,422..1,652,428(+)
Genome classification: Core
Product Description: DNA gyrase subunit B
SignalP Peptide: MNVRFFKSLSLFIFFVKGVILVVQA
# Transmembrane Domains: 0
EC Numbers: 5.6.2.2 (DNA topoisomerase (ATP-hydrolyzing));5.99.1.3 (Transferred entry: 5.6.2.2)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Function | GO:0005524 | ATP binding |
| Function | GO:0016887 | ATP hydrolysis activity |
| Function | GO:0003918 | DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity |
| Function | GO:0046983 | protein dimerization activity |
| Process | GO:0006265 | DNA topological change |
| 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 | possibly expressed | 0.08 | 0.96 |
| Trophozoite | expressed | 0.59 | 0.66 |
| Schizont | expressed | 0.36 | 0.79 |
| Gametocyte | expressed | 0.40 | 0.77 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1239500
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: 0.188 | MFS: -2.708 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1454000)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I528
"Best" AlphaFill ligand hit: ANP (phosphoaminophosphonic acid-adenylate ester, Local RMSD=0.05) with 4WUB (Global RMSD=1.81)
BRENDA EC Inhibitors:
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P9WG45 | DNA gyrase subunit B | OMA, OrthoMCL BLAST | CHEMBL4238919CHEMBL4238919CHEMBL4250651CHEMBL4250651... | |
| P0C559 | DNA gyrase subunit B | OMA, OrthoMCL BLAST | CHEMBL3259858CHEMBL3263620CHEMBL3263621CHEMBL3263585... | |
| P0AES6 | DNA gyrase subunit B | Escherichia coli | OMA, OrthoMCL BLAST | CHEMBL4097472CHEMBL4076393CHEMBL4064127CHEMBL4104625... |
| P0A0K8 | DNA gyrase subunit B | Staphylococcus aureus | OMA, OrthoMCL BLAST | N-(4-(4-Hydrazinyl-4-oxobutanamido)phenyl)-5-methylfuran-2-carboxamide (22)N-(4-(4-Hydrazinyl-4-oxobutanamido)phenyl)-5-methylthiophene-2-carboxamide (25)NOVOBIOCINMoxifl-oxacin... |
| P66936 | DNA gyrase subunit B | OMA, OrthoMCL BLAST | CHEMBL187677 | |
| P0A4L9 | DNA gyrase subunit B | Streptococcus pneumoniae | OMA, OrthoMCL BLAST | CHEMBL565750CHEMBL578149CHEMBL583438CHEMBL583440... |
| Q7X1P7 | DNA topoisomerase (ATP-hydrolyzing) | Streptococcus pneumoniae | OrthoMCL BLAST | CHEMBL565750CHEMBL578149CHEMBL583438CHEMBL583440... |
| Q2FYS5 | DNA topoisomerase 4 subunit A/B | OrthoMCL BLAST | CHEMBL3329317CHEMBL3329319CHEMBL2221212US9040542, 23... | |
| P20083 | DNA topoisomerase 4 subunit B | Escherichia coli | OrthoMCL BLAST | CHEMBL3329317CHEMBL3329318CHEMBL4279313CHEMBL4294536... |
Ortholog Group (OrthoMCL): OG6_100284
Most Similar Human Ortholog: J3KTB7
TM-align score: 0.63 | RMSD: 2.81
Seq Identity: 0.26 | Length: 113 / 1006
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000077097 | DNA topoisomerase II beta |
| ENSG00000131747 | DNA topoisomerase II alpha |
Protein Length: 1006 | Molecular Weight (kDa): 116.107
UniProt ID(s): Q8I528
PDB ID(s): None
Isoelectric Point: 9.59
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000565 | DNA topoisomerase, type IIA, subunit B |
| InterPro | IPR001241 | DNA topoisomerase, type IIA |
| InterPro | IPR002288 | DNA gyrase B subunit, C-terminal |
| InterPro | IPR003594 | Histidine kinase/HSP90-like ATPase |
| InterPro | IPR006171 | TOPRIM domain |
| InterPro | IPR013506 | DNA topoisomerase, type IIA, subunit B, domain 2 |
| InterPro | IPR013760 | DNA topoisomerase, type IIA-like domain superfamily |
| InterPro | IPR018522 | DNA topoisomerase, type IIA, conserved site |
| InterPro | IPR020568 | Ribosomal protein S5 domain 2-type fold |
| InterPro | IPR036890 | Histidine kinase/HSP90-like ATPase superfamily |
| PFam | PF00204 | DNA topoisomerase, type IIA, subunit B, domain 2 |
| PFam | PF00986 | DNA gyrase B subunit, C-terminal |
| PFam | PF01751 | TOPRIM domain |
| PFam | PF02518 | Histidine kinase/HSP90-like ATPase |
| Superfamily | SSF54211 | Ribosomal protein S5 domain 2-type fold |
| Superfamily | SSF55874 | Histidine kinase/HSP90-like ATPase superfamily |
| Superfamily | SSF56719 | DNA topoisomerase, type IIA-like domain superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 6 | 67 | 32 | 75 |
| disruptive | 32 | 112 | 53 | 190 |
| missense | 22 | 107 | 51 | 169 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 14 | 138 | 40 | 64 |
| disruptive | 48 | 252 | 106 | 260 |
| missense | 32 | 214 | 95 | 192 |
PlasmoDB Total SNPs: 155
Non-coding: 109 | Synonymous: 29 | Nonsynonymous: 17 | Stop Codon: 0
| 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 |
| 17220464 | Molecular cloning of apicoplast-targeted Plasmodium falciparum DNA gyrase genes:unique intrinsic ATPase activity and ATP-independent dimerization of PfGyrBsubunit. | Dar MA, Sharma A, Mondal N, Dhar SK | 10.1128/EC.00357-06 |
| 17499371 | Nuclear gyrB encodes a functional subunit of the Plasmodium falciparum gyrasethat is involved in apicoplast DNA replication. | Raghu Ram EV, Kumar A, ..., Habib S | https://pubmed.ncbi.nlm.nih.gov/17499371/ |
| 19700639 | A unique 45-amino-acid region in the toprim domain of Plasmodium falciparumgyrase B is essential for its activity. | Dar A, Prusty D, Mondal N, Dhar SK | 10.1128/EC.00149-09 |
| 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 |
| 34339271 | Inhibitory Compounds Targeting Plasmodium falciparum Gyrase B. | Pakosz Z, Lin TY, ..., Heddle JG | 10.1128/AAC.00267-21 |
| 34716632 | Role of unique loops in oligomerization and ATPase function of Plasmodiumfalciparum gyrase B. | Purushothaman M, Dhar SK, Natesh R | 10.1002/pro.4217 |
| 38392303 | Friend or Foe: Protein Inhibitors of DNA Gyrase | Ruan S, Tu CH, Bourne CR | 10.3390/biology13020084 |
| 38230352 | Comparative molecular profiling of multidrug-resistant Pseudomonas aeruginosaidentifies novel mutations in regional clinical isolates from South India | Menon ND, Somanath P, ..., Kumar GB | 10.1093/jacamr/dlae001 |