DNA gyrase subunit A

UniProt P0AES4 Organism Escherichia coli (strain K12) Gene JW2225, b2231, gyrA, hisW, nalA, parD EC 5.6.2.2

Also known as: JW2225, b2231, gyrA, hisW, nalA, parD

Function

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. This makes better substrates for topoisomerase IV (ParC and ParE) which is the main enzyme that unlinks newly replicated chromosomes in E.coli. Gyrase catalyzes the interconversion of other topological isomers of dsDNA rings, including catenanes. Relaxes negatively supercoiled DNA in an ATP-independent manner. 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. 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. 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.

Classification

Family (Pfam): PF03989 DNA_gyraseA_C, PF00521 DNA_topoisoIV
InterPro: GyrA, GyrA/parC_rep, Gyrase/topoIV_suA_C, Topo_IIA-like_dom_sf, Topo_IIA_A/C_ab, Topo_IIA_A_a_sf, Topo_IIA_dom_A, Type_II_DNA_Topoisomerases
Functional cluster: GroEL/Cpn60 Chaperonins

Experimental structures · PDB · 20

1AB4 X-ray 2.80A
1X75 X-ray 2.80A
1ZI0 X-ray 2.60A
2Y3P X-ray 2.62A
3NUH X-ray 3.10A
4ELY X-ray 1.93A
6RKS EM 4.00A
6RKU EM 4.00A
6RKV EM 4.60A
6RKW EM 6.60A
7Z9C EM 3.06A
7Z9G EM 3.25A
… and 8 more

A predicted model is available from AlphaFold.

Gene Ontology · 17

Drugs targeting this protein · 29

ALATROFLOXACIN MESYLATE inhibitor
MOXIFLOXACIN HYDROCHLORIDE inhibitor
TROVAFLOXACIN MESYLATE inhibitor
BESIFLOXACIN HYDROCHLORIDE inhibitor
CIPROFLOXACIN HYDROCHLORIDE inhibitor
CINOXACIN inhibitor
NEMONOXACIN inhibitor
PRADOFLOXACIN inhibitor
ACORAFLOXACIN inhibitor
IBAFLOXACIN inhibitor
LOMEFLOXACIN HYDROCHLORIDE inhibitor
DELAFLOXACIN MEGLUMINE inhibitor
TEMAFLOXACIN HYDROCHLORIDE inhibitor
ZABOFLOXACIN inhibitor
PAZUFLOXACIN inhibitor
PEFLOXACIN inhibitor
GARENOXACIN MESYLATE inhibitor
GEPOTIDACIN inhibitor
NADIFLOXACIN inhibitor
SITAFLOXACIN inhibitor
OFLOXACIN inhibitor
PRULIFLOXACIN inhibitor
TROVAFLOXACIN inhibitor
RIFAQUIZINONE inhibitor
NALIDIXIC ACID inhibitor
DIFLOXACIN HYDROCHLORIDE inhibitor
CIPROFLOXACIN inhibitor
SPARFLOXACIN inhibitor
NORFLOXACIN inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

DNA gyrase subunit B 18 shared papers
Toxin CcdB 4 shared papers
DNA gyrase subunit A 1 shared papers
DNA topoisomerase 4 subunit A 1 shared papers
DNA topoisomerase 4 subunit B 1 shared papers
Antitoxin CcdA 3 shared papers
Uncharacterized protein YfaA 1 shared papers
DNA gyrase subunit A 1 shared papers
DNA gyrase subunit B 1 shared papers
DNA topoisomerase 4 subunit B 2 shared papers
DNA gyrase subunit B 1 shared papers
Pentapeptide repeat protein QnrB4 1 shared papers

Literature · 36 cited papers

Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE), Part II: development of inhibitors with broad spectrum, Gram-negative antibacterial activity. Bioorg. Med. Chem. Lett. · 2013
Mechanisms for defining supercoiling set point of DNA gyrase orthologs: I. A nonconserved acidic C-terminal tail modulates Escherichia coli gyrase activity. J. Biol. Chem. · 2012
Mechanisms for defining supercoiling set point of DNA gyrase orthologs: II. The shape of the GyrA subunit C-terminal domain (CTD) is not a sole determinant for controlling supercoiling efficiency. J. Biol. Chem. · 2012
Discovery of pyrazolthiazoles as novel and potent inhibitors of bacterial gyrase. Bioorg. Med. Chem. Lett. · 2010
A crystal structure of the bifunctional antibiotic simocyclinone D8, bound to DNA gyrase. Science · 2009
The pentapeptide repeat proteins MfpAMt and QnrB4 exhibit opposite effects on DNA gyrase catalytic reactions and on the ternary gyrase-DNA-quinolone complex. J. Bacteriol. · 2009
DNA gyrase requires DNA for effective two-site coordination of divalent metal ions: further insight into the mechanism of enzyme action. Biochemistry · 2008
Growth rate toxicity phenotypes and homeostatic supercoil control differentiate Escherichia coli from Salmonella enterica serovar Typhimurium. J. Bacteriol. · 2007
Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol. Syst. Biol. · 2006
The 'GyrA-box' is required for the ability of DNA gyrase to wrap DNA and catalyze the supercoiling reaction. J. Biol. Chem. · 2006
A superhelical spiral in the Escherichia coli DNA gyrase A C-terminal domain imparts unidirectional supercoiling bias. J. Biol. Chem. · 2005
Molecular basis of gyrase poisoning by the addiction toxin CcdB. J. Mol. Biol. · 2005
… and 24 more in the literature graph

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