UniProtKB - P0AES4 (GYRA_ECOLI)
DNA gyrase subunit A
gyrA
Functioni
A type II topoisomerase that negatively supercoils closed circular double-stranded (ds) DNA in an ATP-dependent manner to maintain chromosomes in an underwound state (PubMed:3031051, PubMed:186775, PubMed:7811004, PubMed:9148951, PubMed:12051842, PubMed:18642932, PubMed:19060136, PubMed:20356737, PubMed:22457353, PubMed:23294697, PubMed:19965760).
This makes better substrates for topoisomerase IV (ParC and ParE) which is the main enzyme that unlinks newly replicated chromosomes in E.coli (PubMed:9334322).
Gyrase catalyzes the interconversion of other topological isomers of dsDNA rings, including catenanes (PubMed:22457352).
Relaxes negatively supercoiled DNA in an ATP-independent manner (PubMed:337300).
E.coli gyrase has higher supercoiling activity than many other bacterial gyrases; at comparable concentrations E.coli gyrase introduces more supercoils faster than M.tuberculosis gyrase, while M.tuberculosis gyrase has higher decatenation than supercoiling activity compared to E.coli (PubMed:22457352).
E.coli makes 15% more negative supercoils in pBR322 plasmid DNA than S.typhimurium; the S.typhimurium GyrB subunit is toxic in E.coli, while the E.coli copy can be expressed in S.typhimurium even though the 2 subunits have 777/804 residues identical (PubMed:17400739).
The enzymatic differences between E.coli gyrase and topoisomerase IV are largely due to the GyrA C-terminal domain (approximately residues 524-841) and specifically the GyrA-box (PubMed:8962066, PubMed:16332690).
17 PublicationsNegative supercoiling favors strand separation, and DNA replication, transcription, recombination and repair, all of which involve strand separation. Type II topoisomerases break and join 2 DNA strands simultaneously in an ATP-dependent manner.
Miscellaneous
Catalytic activityi
- ATP-dependent breakage, passage and rejoining of double-stranded DNA.UniRule annotation5 Publications EC:5.6.2.2
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 122 | O-(5'-phospho-DNA)-tyrosine intermediateUniRule annotation1 Publication | 1 |
GO - Molecular functioni
- ATP binding Source: GO_Central
- ATP-dependent activity, acting on DNA Source: EcoliWiki
- DNA binding Source: EcoliWiki
- DNA negative supercoiling activity Source: UniProtKB
- DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity Source: CACAO
- identical protein binding Source: IntAct
GO - Biological processi
- DNA-dependent DNA replication Source: UniProtKB-UniRule
- DNA topological change Source: ComplexPortal
- negative regulation of DNA-dependent DNA replication Source: ComplexPortal
- response to antibiotic Source: UniProtKB-KW
- transcription, DNA-templated Source: EcoliWiki
Keywordsi
Molecular function | DNA-binding, Isomerase, Topoisomerase |
Biological process | Antibiotic resistance |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BioCyci | EcoCyc:EG10423-MONOMER |
Names & Taxonomyi
Protein namesi | Recommended name: DNA gyrase subunit AUniRule annotation (EC:5.6.2.2UniRule annotation5 Publications) |
Gene namesi | Name:gyrAUniRule annotation Synonyms:hisW, nalA1 Publication, parD Ordered Locus Names:b2231, JW2225 |
Organismi | Escherichia coli (strain K12) |
Taxonomic identifieri | 83333 [NCBI] |
Taxonomic lineagei | Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacterales › Enterobacteriaceae › Escherichia › |
Proteomesi |
|
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm UniRule annotation
Cytosol
- cytosol Source: EcoCyc
Other locations
- chromosome Source: InterPro
- cytoplasm Source: EcoliWiki
- DNA gyrase complex Source: ComplexPortal
- DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex Source: GO_Central
- membrane Source: UniProtKB
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 32 | R → A or Q: Nearly abolishes DNA supercoiling. Reduces quinolone-induced DNA cleavage and relaxation. 1 Publication | 1 | |
Mutagenesisi | 47 | R → Q: Nearly abolishes DNA supercoiling. Reduces quinolone-induced DNA cleavage. Slightly reduces DNA relaxation. 1 Publication | 1 | |
Mutagenesisi | 78 | H → A: Nearly abolishes DNA supercoiling. Reduces quinolone-induced DNA cleavage and DNA relaxation. 1 Publication | 1 | |
Mutagenesisi | 80 | H → A: Reduces DNA supercoiling. Slightly reduces quinolone-induced DNA cleavage. No effect on DNA relaxation. 1 Publication | 1 | |
Mutagenesisi | 83 | S → A: Resistant to fluoroquinolones. 1 Publication | 1 | |
Mutagenesisi | 106 | Q → R: Resistant to fluoroquinolones. 1 Publication | 1 | |
Mutagenesisi | 462 | R → C in gyrA462; resistant to cytotoxic protein CcdB, but not to the quinoline antibiotic enoxacin, has no effect on DNA supercoiling. Does not interact with CcdB. 2 Publications | 1 | |
Mutagenesisi | 560 – 566 | QRRGGKG → AAAAAAA: Loss of gyrase-mediated DNA wrapping, nearly complete loss of DNA supercoiling activity, no change in DNA supercoil relaxation or DNA decatenation activity. 1 Publication | 7 | |
Mutagenesisi | 560 – 566 | Missing : Loss of gyrase-mediated DNA wrapping, nearly complete loss of DNA supercoiling activity, no change in DNA supercoil relaxation or DNA decatenation activity. 1 Publication | 7 | |
Mutagenesisi | 842 – 856 | Missing : Gains ability to wrap DNA around itself in the absence of GyrB; holoenzyme gains ability to wrap DNA in the absence of ATP analogs, but reduces ATP-dependent supercoiling activity 50-fold, DNA is not as extensively negatively supercoiled, has 10-fold less ATP-independent negative supercoiled DNA relaxation activity, no change in ATPase activity of holoenzyme, no change in decatenation ability. Isolated CTD gains ability to wrap DNA around itself in the absence of GyrB, binds DNA better than wild-type CTD. 2 PublicationsAdd BLAST | 15 | |
Mutagenesisi | 854 – 875 | Missing : Isolated CTD gains ability to wrap DNA around itself in the absence of GyrB, binds DNA better than wild-type CTD. 1 PublicationAdd BLAST | 22 |
Chemistry databases
ChEMBLi | CHEMBL1858 |
DrugBanki | DB00537, Ciprofloxacin DB11943, Delafloxacin |
DrugCentrali | P0AES4 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed1 Publication | |||
ChainiPRO_0000145232 | 2 – 875 | DNA gyrase subunit AAdd BLAST | 874 |
Proteomic databases
jPOSTi | P0AES4 |
PaxDbi | P0AES4 |
PRIDEi | P0AES4 |
2D gel databases
SWISS-2DPAGEi | P0AES4 |
Interactioni
Subunit structurei
Heterotetramer, composed of two GyrA and two GyrB chains (PubMed:9148951, PubMed:12051842). In the heterotetramer, GyrA contains the active site tyrosine that forms a transient covalent intermediate with the DNA, while GyrB binds cofactors and catalyzes ATP hydrolysis (PubMed:12051842, PubMed:18642932, PubMed:19965760, PubMed:9148951). Can form a 2:2 complex with toxin CcdB in which GyrA is inactive; rejuvenation of GyrA2CcdB2 is effected by CcdA (PubMed:15854646, PubMed:1324324, PubMed:8254658, PubMed:8604132).
8 PublicationsBinary interactionsi
P0AES4
With | #Exp. | IntAct |
---|---|---|
ccdB [P62554] | 3 | EBI-547129,EBI-25647730 |
itself | 6 | EBI-547129,EBI-547129 |
gyrB [P0AES6] | 7 | EBI-547129,EBI-541911 |
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 4262132, 294 interactors |
ComplexPortali | CPX-2177, GyrA-GyrB DNA Gyrase complex CPX-5906, CcdB-poisoned gyrase complex |
DIPi | DIP-36179N |
IntActi | P0AES4, 55 interactors |
MINTi | P0AES4 |
STRINGi | 511145.b2231 |
Chemistry databases
BindingDBi | P0AES4 |
Structurei
Secondary structure
3D structure databases
SMRi | P0AES4 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P0AES4 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 531 – 841 | C-terminal domain (CTD)1 PublicationAdd BLAST | 311 | |
Regioni | 841 – 875 | DisorderedSequence analysisAdd BLAST | 35 | |
Regioni | 842 – 875 | Acidic tail1 PublicationAdd BLAST | 34 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 560 – 566 | GyrA-box1 PublicationUniRule annotation | 7 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 845 – 875 | Acidic residuesSequence analysisAdd BLAST | 31 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | COG0188, Bacteria |
HOGENOMi | CLU_002977_6_1_6 |
InParanoidi | P0AES4 |
PhylomeDBi | P0AES4 |
Family and domain databases
CDDi | cd00187, TOP4c, 1 hit |
Gene3Di | 1.10.268.10, 1 hit 2.120.10.90, 1 hit 3.90.199.10, 1 hit |
HAMAPi | MF_01897, GyrA, 1 hit |
InterProi | View protein in InterPro IPR005743, GyrA IPR006691, GyrA/parC_rep IPR035516, Gyrase/topoIV_suA_C IPR013760, Topo_IIA-like_dom_sf IPR013758, Topo_IIA_A/C_ab IPR013757, Topo_IIA_A_a_sf IPR002205, Topo_IIA_dom_A |
Pfami | View protein in Pfam PF03989, DNA_gyraseA_C, 6 hits PF00521, DNA_topoisoIV, 1 hit |
SMARTi | View protein in SMART SM00434, TOP4c, 1 hit |
SUPFAMi | SSF101904, SSF101904, 1 hit SSF56719, SSF56719, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MSDLAREITP VNIEEELKSS YLDYAMSVIV GRALPDVRDG LKPVHRRVLY
60 70 80 90 100
AMNVLGNDWN KAYKKSARVV GDVIGKYHPH GDSAVYDTIV RMAQPFSLRY
110 120 130 140 150
MLVDGQGNFG SIDGDSAAAM RYTEIRLAKI AHELMADLEK ETVDFVDNYD
160 170 180 190 200
GTEKIPDVMP TKIPNLLVNG SSGIAVGMAT NIPPHNLTEV INGCLAYIDD
210 220 230 240 250
EDISIEGLME HIPGPDFPTA AIINGRRGIE EAYRTGRGKV YIRARAEVEV
260 270 280 290 300
DAKTGRETII VHEIPYQVNK ARLIEKIAEL VKEKRVEGIS ALRDESDKDG
310 320 330 340 350
MRIVIEVKRD AVGEVVLNNL YSQTQLQVSF GINMVALHHG QPKIMNLKDI
360 370 380 390 400
IAAFVRHRRE VVTRRTIFEL RKARDRAHIL EALAVALANI DPIIELIRHA
410 420 430 440 450
PTPAEAKTAL VANPWQLGNV AAMLERAGDD AARPEWLEPE FGVRDGLYYL
460 470 480 490 500
TEQQAQAILD LRLQKLTGLE HEKLLDEYKE LLDQIAELLR ILGSADRLME
510 520 530 540 550
VIREELELVR EQFGDKRRTE ITANSADINL EDLITQEDVV VTLSHQGYVK
560 570 580 590 600
YQPLSEYEAQ RRGGKGKSAA RIKEEDFIDR LLVANTHDHI LCFSSRGRVY
610 620 630 640 650
SMKVYQLPEA TRGARGRPIV NLLPLEQDER ITAILPVTEF EEGVKVFMAT
660 670 680 690 700
ANGTVKKTVL TEFNRLRTAG KVAIKLVDGD ELIGVDLTSG EDEVMLFSAE
710 720 730 740 750
GKVVRFKESS VRAMGCNTTG VRGIRLGEGD KVVSLIVPRG DGAILTATQN
760 770 780 790 800
GYGKRTAVAE YPTKSRATKG VISIKVTERN GLVVGAVQVD DCDQIMMITD
810 820 830 840 850
AGTLVRTRVS EISIVGRNTQ GVILIRTAED ENVVGLQRVA EPVDEEDLDT
860 870
IDGSAAEGDD EIAPEVDVDD EPEEE
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 67 | A → S in PPA-10; quinolone-resistant. 1 Publication | 1 | |
Natural varianti | 81 | G → C in NAL-97; quinolone-resistant. 1 Publication | 1 | |
Natural varianti | 83 | S → L in NAL-51, NAL-112, NAL-118, NAL-119 and strains 58, 158, 218, 231 and 235; quinolone-resistant. 2 Publications | 1 | |
Natural varianti | 83 | S → W in PPA-18 and strains 233 and 227; quinolone-resistant. 3 Publications | 1 | |
Natural varianti | 84 | A → P in PPA-05; quinolone-resistant. 1 Publication | 1 | |
Natural varianti | 87 | D → N in NAL-113 and OV6; quinolone-resistant. 2 Publications | 1 | |
Natural varianti | 87 | D → V in strain: 202; partially quinolone-resistant. 1 Publication | 1 | |
Natural varianti | 106 | Q → H in NAL-89; quinolone-resistant. 1 Publication | 1 | |
Natural varianti | 678 | D → E in strain: 227. 1 Publication | 1 | |
Natural varianti | 798 | I → IMMI in strain: OV6; quinolone-resistant. 1 Publication | 1 | |
Natural varianti | 828 | A → S in strain: 227. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X06373 Genomic DNA Translation: CAA29676.1 X06744 Genomic DNA Translation: CAA29919.1 M15631 Genomic DNA Translation: AAA23948.1 U00096 Genomic DNA Translation: AAC75291.1 AP009048 Genomic DNA Translation: BAA16048.1 Y00544 Genomic DNA Translation: CAA68611.1 |
PIRi | S02340, ITECAP |
RefSeqi | NP_416734.1, NC_000913.3 WP_001281242.1, NZ_LN832404.1 |
Genome annotation databases
EnsemblBacteriai | AAC75291; AAC75291; b2231 BAA16048; BAA16048; BAA16048 |
GeneIDi | 66673880 946614 |
KEGGi | ecj:JW2225 eco:b2231 |
PATRICi | fig|1411691.4.peg.4 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X06373 Genomic DNA Translation: CAA29676.1 X06744 Genomic DNA Translation: CAA29919.1 M15631 Genomic DNA Translation: AAA23948.1 U00096 Genomic DNA Translation: AAC75291.1 AP009048 Genomic DNA Translation: BAA16048.1 Y00544 Genomic DNA Translation: CAA68611.1 |
PIRi | S02340, ITECAP |
RefSeqi | NP_416734.1, NC_000913.3 WP_001281242.1, NZ_LN832404.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1AB4 | X-ray | 2.80 | A | 30-522 | [»] | |
1X75 | X-ray | 2.80 | A/B | 363-494 | [»] | |
1ZI0 | X-ray | 2.60 | A/B | 535-841 | [»] | |
2Y3P | X-ray | 2.62 | A/B | 2-523 | [»] | |
3NUH | X-ray | 3.10 | A | 1-525 | [»] | |
4ELY | X-ray | 1.93 | A/B | 363-497 | [»] | |
6RKS | electron microscopy | 4.00 | A/C | 1-875 | [»] | |
6RKU | electron microscopy | 4.00 | A/C | 1-875 | [»] | |
6RKV | electron microscopy | 4.60 | A/C | 1-875 | [»] | |
6RKW | electron microscopy | 6.60 | A/C | 1-875 | [»] | |
SMRi | P0AES4 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 4262132, 294 interactors |
ComplexPortali | CPX-2177, GyrA-GyrB DNA Gyrase complex CPX-5906, CcdB-poisoned gyrase complex |
DIPi | DIP-36179N |
IntActi | P0AES4, 55 interactors |
MINTi | P0AES4 |
STRINGi | 511145.b2231 |
Chemistry databases
BindingDBi | P0AES4 |
ChEMBLi | CHEMBL1858 |
DrugBanki | DB00537, Ciprofloxacin DB11943, Delafloxacin |
DrugCentrali | P0AES4 |
2D gel databases
SWISS-2DPAGEi | P0AES4 |
Proteomic databases
jPOSTi | P0AES4 |
PaxDbi | P0AES4 |
PRIDEi | P0AES4 |
Genome annotation databases
EnsemblBacteriai | AAC75291; AAC75291; b2231 BAA16048; BAA16048; BAA16048 |
GeneIDi | 66673880 946614 |
KEGGi | ecj:JW2225 eco:b2231 |
PATRICi | fig|1411691.4.peg.4 |
Organism-specific databases
EchoBASEi | EB0418 |
Phylogenomic databases
eggNOGi | COG0188, Bacteria |
HOGENOMi | CLU_002977_6_1_6 |
InParanoidi | P0AES4 |
PhylomeDBi | P0AES4 |
Enzyme and pathway databases
BioCyci | EcoCyc:EG10423-MONOMER |
Miscellaneous databases
EvolutionaryTracei | P0AES4 |
PROi | PR:P0AES4 |
Family and domain databases
CDDi | cd00187, TOP4c, 1 hit |
Gene3Di | 1.10.268.10, 1 hit 2.120.10.90, 1 hit 3.90.199.10, 1 hit |
HAMAPi | MF_01897, GyrA, 1 hit |
InterProi | View protein in InterPro IPR005743, GyrA IPR006691, GyrA/parC_rep IPR035516, Gyrase/topoIV_suA_C IPR013760, Topo_IIA-like_dom_sf IPR013758, Topo_IIA_A/C_ab IPR013757, Topo_IIA_A_a_sf IPR002205, Topo_IIA_dom_A |
Pfami | View protein in Pfam PF03989, DNA_gyraseA_C, 6 hits PF00521, DNA_topoisoIV, 1 hit |
SMARTi | View protein in SMART SM00434, TOP4c, 1 hit |
SUPFAMi | SSF101904, SSF101904, 1 hit SSF56719, SSF56719, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | GYRA_ECOLI | |
Accessioni | P0AES4Primary (citable) accession number: P0AES4 Secondary accession number(s): P09097 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 20, 2005 |
Last sequence update: | December 20, 2005 | |
Last modified: | February 23, 2022 | |
This is version 152 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families