About Gene List

PF3D7_1223300 (GyrA)

Genome location: Pf3D7_12_v3:934,432..938,673(-)

Genome classification: Core

Function and Localization

Product Description: DNA gyrase subunit A

SignalP Peptide: N/A

# 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:0009330 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex
Component GO:0020011 apicoplast
Function GO:0005524 ATP binding
Function GO:0003677 DNA binding
Function GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity
Process GO:0006265 DNA topological change

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 0.26 0.87
Trophozoite not expressed 0.70 0.61
Schizont not expressed 0.60 0.65
Gametocyte not expressed 0.36 0.79

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1223300

Resistome Missense Mutations: None

Resistome Compounds with Missense Mutations: None

Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Non - Mutable in CDS

MIS: 0.119 | MFS: -3.116 | #Insertions: 0

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8I0X3

"Best" AlphaFill ligand hit: EVP (etoposide, Local RMSD=0.01) with 5CDP (Global RMSD=1.74)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
5.6.2.2 DNA topoisomerase (ATP-hydrolysing) BRENDA SOAP query unsuccessful
5.99.1.3 DNA topoisomerase (ATP-hydrolysing) No BRENDA inhibitors

Orthology to BindingDB Entries:

UniProt Protein Name Species Homology Source BindingDB Ligands
P0AES4 DNA gyrase subunit A/B Escherichia coli OrthoMCL, OrthoMCL BLAST NOVOBIOCINBenzimidazole urea analogue, 2Benzimidazole urea analogue, 3Benzimidazole urea analogue, 4...
P05653 DNA gyrase subunit A/B Bacillus subtilis OrthoMCL, OrthoMCL BLAST PD125275Ciprofloxacin
P9WG47 DNA gyrase subunit A/B OrthoMCL, OrthoMCL BLAST NOVOBIOCINMOXIFLOXACINGATIFLOXACINACH-702
P0C1U9 DNA topoisomerase 4 subunit A Staphylococcus aureus OrthoMCL BLAST CHEMBL202753CHEMBL379022CHEMBL425234CHEMBL203851...
Q2FYS4 DNA topoisomerase 4 subunit A/B OrthoMCL BLAST US9040542, 23
Q45066 DNA topoisomerase 4 subunit A [V210L]/B Bacillus subtilis OrthoMCL BLAST PD125275Ciprofloxacin
Q931S2 DNA topoisomerase 4 subunit A OrthoMCL BLAST CHEMBL363725CHEMBL186870CHEMBL184489CHEMBL365638...
P20831 DNA gyrase subunit A/B Staphylococcus aureus OrthoMCL BLAST NOVOBIOCINBenzimidazole carbamate analogue, 1Benzimidazole urea analogue, 2Benzimidazole urea analogue, 3...
P0AFI2 DNA topoisomerase 4 subunit A Escherichia coli OrthoMCL BLAST NOVOBIOCINBenzimidazole urea analogue, 2Benzimidazole urea analogue, 3Benzimidazole urea analogue, 4...
Q47245 DNA gyrase subunit A OrthoMCL BLAST OFLOXACINMoxifl-oxacinCHEMBL4459270CHEMBL4470688...

Orthology Information

Ortholog Group (OrthoMCL): OG6_105177

No human ortholog(s)

Protein Information

Protein Length: 1222 | Molecular Weight (kDa): 143.144

UniProt ID(s): Q8I0X3

PDB ID(s): None

Isoelectric Point: 9.87

Protein Domain Annotations:

Source Family ID Description
InterPro IPR002205 DNA topoisomerase, type IIA, subunit A/C-terminal
InterPro IPR006691 DNA gyrase/topoisomerase IV, subunit A, C-terminal repeat
InterPro IPR013760 DNA topoisomerase, type IIA-like domain superfamily
InterPro IPR035516 DNA gyrase/topoisomerase IV, subunit A, C-terminal
PFam PF00521 DNA topoisomerase, type IIA, subunit A/C-terminal
PFam PF03989 DNA gyrase/topoisomerase IV, subunit A, C-terminal repeat
Superfamily SSF101904 DNA gyrase/topoisomerase IV, subunit A, C-terminal
Superfamily SSF56719 DNA topoisomerase, type IIA-like domain superfamily

Genetic Variation

MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 10 37 15 57
disruptive 13 72 48 125
missense 9 67 44 106

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 13 73 38 58
disruptive 30 173 94 219
missense 14 139 84 169

PlasmoDB Total SNPs: 99

Non-coding: 25 | Synonymous: 57 | Nonsynonymous: 17 | Stop Codon: 0

Associated Publications

PMID Title Authors DOI/Link
12368864 Genome sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Hall N, ..., Barrell B 10.1038/nature01097
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/
22474358 Gene selective mRNA cleavage inhibits the development of Plasmodium falciparum. Augagneur Y, Wesolowski D, ..., Ben Mamoun C 10.1073/pnas.1203516109
26566222 Investigating the Roles of the C-Terminal Domain of Plasmodium falciparum GyrA. Nagano S, Seki E, ..., Heddle JG 10.1371/journal.pone.0142313
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
38349187 Detection of resistance to macrolides and fluoroquinolones in Mycoplasmagenitalium by targeted next-generation sequencing Chiribau CB, Schmedes S, ..., Crowe SR 10.1128/spectrum.03845-23
38392303 Friend or Foe: Protein Inhibitors of DNA Gyrase Ruan S, Tu CH, Bourne CR 10.3390/biology13020084
38396892 Antibiotic Combination to Effectively Postpone or Inhibit the In Vitro Inductionand Selection of Levofloxacin-Resistant Mutants in Elizabethkingia anophelis Lee CC, Lai CH, ..., Lin JN 10.3390/ijms25042215