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Information on EC 5.6.2.2 - DNA topoisomerase (ATP-hydrolysing) and Organism(s) Staphylococcus aureus and UniProt Accession Q99XG5
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5.6.2.2 DNA topoisomerase (ATP-hydrolysing)IUBMB Comments
The enzyme can introduce negative superhelical turns into double-stranded circular DNA. One unit has nicking-closing activity, and another catalyses super-twisting and hydrolysis of ATP (cf. EC 5.6.2.1 DNA topoisomerase).
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Word Map
- 5.6.2.2
- myosin
- na+
- adp
- sarcoplasmic
- cardiac
- actin
- etoposide
- helicase
- chromatin
- strand
- triphosphatase
- ouabain
-
multidrug
-
supercoiling
- leukemia
-
contractile
- fiber
- doxorubicin
- erythrocyte
- p-glycoprotein
-
single-stranded
-
poison
-
quinolone
- myofibrillar
- vanadate
- fluoroquinolones
- actomyosin
- ciprofloxacin
-
unwind
- microtubule
- duplex
- hsp90
- vacuolar
-
dna-dependent
- calmodulin
- serca
- anthracyclines
-
ca2+-dependent
- camptothecin
- myofibril
- thapsigargin
- kinesins
- verapamil
- nucleosome
- troponin
- dyneins
- fork
-
sliding
-
isometric
-
electrogenic
- medicine
- diagnostics
- analysis
- drug development
- pharmacology
The taxonomic range for the selected organisms is: Staphylococcus aureus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
atpase, topoisomerase ii, dna gyrase, topo ii, gyrase, top2a, dna topoisomerase ii, topoisomerase iialpha, topo iialpha, topoisomerase ii alpha, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
DNA gyrase
DNA topoisomerase II
-
-
-
-
DNA topoisomerase type II
-
-
-
-
Isomerase, deoxyribonucleate topo-, II
-
-
-
-
NP170 proteins
-
-
-
-
Nuclear proteins 170,000-mol.wt.
-
-
-
-
Protein Gp39
-
-
-
-
Protein Gp52
-
-
-
-
Protein Gp60
-
-
-
-
Proteins , NP170 (specific proteins and subclasses nuclear protein, 170,000-mol.-wt.)
-
-
-
-
PsTopII
-
-
-
-
TOPOII
-
-
-
-
Topoisomerase II
-
-
-
-
Topoisomerase type II
-
-
-
-
topoIV
Type II-DNA-topoisomerase
-
-
-
-
type IIA topoisomerase
DNA gyrase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
isomerization
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
DNA topoisomerase (ATP-hydrolysing)
The enzyme can introduce negative superhelical turns into double-stranded circular DNA. One unit has nicking-closing activity, and another catalyses super-twisting and hydrolysis of ATP (cf. EC 5.6.2.1 DNA topoisomerase).
CAS REGISTRY NUMBER
COMMENTARY
142805-56-9
-
80449-01-0
formerly not distinguished from EC 5.99.1.2
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + relaxed pBR322 DNA
ADP + phosphate + supercoiled pBR322 DNA
-
-
-
?
ATP + supercoiled pBR322 DNA
ADP + phosphate + relaxed pBR322 DNA
-
-
-
?
network of DNA rings + ATP + H2O
monomeric DNA circles + ADP + phosphate
-
decatenation
-
?
supercoiled DNA + ATP + H2O
relaxed DNA + ADP + phosphate
-
relaxation
-
?
supercoiled DNA + ATP + H2O
catenated DNA networks + ADP + phosphate
-
-
-
-
?
supercoiled DNA + ATP + H2O
catenated DNA networks + ADP + phosphate
-
catenation
-
?
additional information
?
-
for DNA cleavage, the correct positioning of the catalytic tyrosine on the CAP domain with respect to the topoisomerase/primase domain seems to be achieved by a rigid body-domain movement, catalytic mechanism and role of the metal-binding TOPRIM domains in catalysis, overview
-
-
?
additional information
?
-
for DNA cleavage, the correct positioning of the catalytic tyrosine on the CAP domain with respect to the topoisomerase/primase domain seems to be achieved by a rigid body-domain movement, catalytic mechanism and role of the metal-binding TOPRIM domains in catalysis, overview
-
-
?
additional information
?
-
-
for DNA cleavage, the correct positioning of the catalytic tyrosine on the CAP domain with respect to the topoisomerase/primase domain seems to be achieved by a rigid body-domain movement, catalytic mechanism and role of the metal-binding TOPRIM domains in catalysis, overview
-
-
?
additional information
?
-
for DNA cleavage, the correct positioning of the catalytic tyrosine on the CAP domain with respect to the topoisomerase/primase domain seems to be achieved by a rigid body-domain movement, catalytic mechanism and role of the metal-binding TOPRIM domains in catalysis, overview
-
-
?
additional information
?
-
for DNA cleavage, the correct positioning of the catalytic tyrosine on the CAP domain with respect to the topoisomerase/primase domain seems to be achieved by a rigid body-domain movement, catalytic mechanism and role of the metal-binding TOPRIM domains in catalysis, overview
-
-
?
additional information
?
-
-
for DNA cleavage, the correct positioning of the catalytic tyrosine on the CAP domain with respect to the topoisomerase/primase domain seems to be achieved by a rigid body-domain movement, catalytic mechanism and role of the metal-binding TOPRIM domains in catalysis, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
required, metal binding structure of wild-type and mutant enzymes, overview
Mn2+
substitution of Mn2+ for Mg2+ increases markedly the stability of the ternary complex of enzyme mutant with inhibitor and metal ion, metal binding structure of wild-type and mutant enzymes, overview
Mg2+
Mn2+
substitution of Mn2+ for Mg2+ increases markedly the stability of the ternary complex of enzyme mutant with inhibitor and metal ion, metal binding structure of wild-type and mutant enzymes, overview
Mg2+
required, metal binding structure of wild-type and mutant enzymes, overview
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
6-methoxy-4-(2-[4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]piperidin-1-yl]ethyl)quinoline-3-carbonitrile
i.e. GSK299423, it shows potent inhibition of supercoiling by DNA gyrase, enzyme binding mode and structure, overview. The inhibitor bridges the DNA and a transient non-catalytic pocket on the 2fold axis at the GyrA dimer interface, and is close to the active sites and luoroquinolone binding sites. In the inhibitor complex the active site seems poised to cleave the DNA, with a single metal ion observed between the topoisomerase/primase domain and the scissile phosphate
Ciprofloxacin
a fluoroquinolone, enzyme binding mode and structure, overview
(2R)-2-[(5Z)-5-[[3-(4-fluorophenoxy)phenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
-
(2S)-2-[(5Z)-4-oxo-5-[(3-phenoxyphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
-
(2S)-2-[(5Z)-4-oxo-5-[(3-[[(2Z)-3-phenylprop-2-en-1-yl]oxy]phenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
-
(2S)-2-[(5Z)-5-([3-[(3,4-dichlorophenyl)methyl]phenyl]methylidene)-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
-
(2S)-2-[(5Z)-5-[(3',4'-dichloro[1,1'-biphenyl]-3-yl)methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
-
(2S)-2-[(5Z)-5-[(3-benzoylphenyl)methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
-
(2S)-2-[(5Z)-5-[(3-benzylphenyl)methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
-
(2S)-2-[(5Z)-5-[([1,1'-biphenyl]-3-yl)methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
-
(2S)-2-[(5Z)-5-[[3-(3,4-dichlorophenoxy)phenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
-
(2S)-2-[(5Z)-5-[[3-(3-chlorophenoxy)phenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
-
(2S)-2-[(5Z)-5-[[3-(benzyloxy)phenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
-
1-(4-nitrobenzylidene)-2-(2-oxo-4-phenyl-2H-benzo[b]pyran-7-yloxy)acetohydrazide
-
-
3-acetyl-2-(4-methoxyphenyl)-5-(2-oxo-4-phenyl-2H-benzo[b]pyran-7-yloxymethyl)-1,3,4-(2H)-oxadiazole
-
-
3-chloro-4-(4-nitrophenyl)-1-[(2-oxo-4-phenyl-2H-benzo[b]pyran-7-yloxy)acetamido] azetidin-2-one
-
-
4-chloro-5-phenyl-1-[(2-oxo-4-phenyl-2H-benzo[b]pyran-7-yloxy)acetamido]pyrrolidin-2-one
-
-
6-methoxy-4-(2-[4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]piperidin-1-yl]ethyl)quinoline-3-carbonitrile
i.e. GSK299423, it shows potent inhibition of supercoiling by DNA gyrase, enzyme binding mode and structure, overview. The inhibitor bridges the DNA and a transient non-catalytic pocket on the 2fold axis at the GyrA dimer interface, and is close to the active sites and luoroquinolone binding sites. In the inhibitor complex the active site seems poised to cleave the DNA, with a single metal ion observed between the topoisomerase/primase domain and the scissile phosphate
ABT-719
-
i.e. A-86719.1 or 8-(3-(S)-aminopyrrolidin-1-yl)-1-cyclopropyl-7-fluoro-9-methyl-4H-4-oxo-quinolizine-3-carboxylic acid hydrochloride monohydrate, in vitro evaluation, 2-pyrisone derivative, MIC90 is 0.000015 mg/ml for strain CiproS, 0.00025 mg/ml for strain CiproR, and 0.001 mg/ml for the methicillin-resistant strain
clinafloxacin
-
MIC90 is 0.00003 mg/ml for strain CiproS, 0.001 mg/ml for strain CiproR, and 0.001 mg/ml for the methicillin-resistant strain
sparfloxacin
-
MIC90 is 0.00006 mg/ml for strain CiproS, 0.016 mg/ml for strain CiproR, and 0.008 mg/ml for the methicillin-resistant strain
y, Namen korrigieren: 4-chloro-5-(furan-2-yl)-1-[(2-oxo-4-phenyl-2H-benzo[b]pyran-7-yloxy)acetamido]pyrrolidin-2-one
-
-
additional information
-
not inhibited by 1-(benzylidene)-2-(2-oxo-4-phenyl-2H-benzo[b]pyran-7-yloxy)acetohydrazide, 3-chloro-4-phenyl-1-[(2-oxo-4-phenyl-2H-benzo[b]pyran-7-yloxy)acetamido]azetidin-2-one, 4-chloro-5-(4-chlorophenyl)-1-[(2-oxo-4-phenyl-2H-benzo[b]pyran-7-yloxy)acetamido] pyrrolidin-2-one, 4-chloro-5-(4-nitrophenyl)-1-[(2-oxo-4-phenyl-2H-benzo[b]pyran-7-yloxy)acetamido] pyrrolidin-2-one, 3-acetyl-2-(furan-2-yl)-5-(2-oxo-4-phenyl-2H-benzo[b]pyran-7-yloxymethyl)-1,3,4-(2H)-oxadiazole, 2-(furan-2-yl)-3-[2-oxo-4-phenyl-2H-benzo[b]pyran-7-yloxyacetamido]-thiazolidin-4-one, and amphotericin B
-
Ciprofloxacin
-
MIC90 is 0.0005 mg/ml for strain CiproS, 0.064 mg/ml for strain CiproR, and 0.128 mg/ml for the methicillin-resistant strain
Ciprofloxacin
a fluoroquinolone, enzyme binding mode and structure, overview
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000014
6-methoxy-4-(2-[4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]piperidin-1-yl]ethyl)quinoline-3-carbonitrile
Staphylococcus aureus
pH not specified in the publication, temperature not specified in the publication
0.031
Ciprofloxacin
Staphylococcus aureus
pH not specified in the publication, temperature not specified in the publication
0.000014
6-methoxy-4-(2-[4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]piperidin-1-yl]ethyl)quinoline-3-carbonitrile
Staphylococcus aureus
pH not specified in the publication, temperature not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
type IIA topoisomerase cleaves and religates DNA to regulate DNA topology
physiological function
type IIA topoisomerase cleaves and religates DNA to regulate DNA topology
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
heterotetramer
Two constructs of 56 and 59 kDa spanning the DNA-cleavage domain of the A subunit of topoisomerase IV from Staphylococcus aureus. All bacterial type IIA topoisomerases are A2B2 heterotetramers containing three discrete subunit interfaces which open and close sequentially in response to ATP binding and hydrolysis in order to effect DNA transport
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant, improved for crystallization, DNA gyrase construct GyrB27-A56(GKdel/Tyr123Phe) in a ternary complex with a 20-bp double-nicked DNA and inhibitor GSK299423 or inhibitor ciprofloxacin, X-ray diffraction structure determination and analysis at 2.1 A and 3.35 A resolution, respectively
first report of crystallization and preliminary X-ray analysis of the DNA-cleavage domain of a topoisomerase IV from a gram positive organism. Sparse-matrix screening used, Crystals of both protein fragments (GrlA56 and GrlA59) display a plate-like morphology and initially grow in tightly packed clusters. Crystallization and X-ray analysis of two different constructs of the A subunit of topoisomerase IV from Staphylococcus aureus (GrlA) are described. With a view to gaining further insight into the mode of inhibition of quinolone antibiotics against this enzyme
recombinant, improved for crystallization, DNA gyrase construct GyrB27-A56(GKdel/Tyr123Phe) in a ternary complex with a 20-bp double-nicked DNA and inhibitor GSK299423 or inhibitor ciprofloxacin, X-ray diffraction structure determination and analysis at 2.1 A and 3.35 A resolution, respectively
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Y123F
site-directed mutagenesis, the Tyr123Phe construct stabilizes a homogenous pre-cleavage conformation trapped by the inhibitor, with a construct that is otherwise demonstrated to be cleavage competent
Y123F
site-directed mutagenesis, the Tyr123Phe construct stabilizes a homogenous pre-cleavage conformation trapped by the inhibitor, with a construct that is otherwise demonstrated to be cleavage competent
additional information
additional information
the small, flexible Greek key or tail domain, residues 544-579, in the GyrB subunit, which does not make contact with the DNA in the crystal structure at 3.5 A resolution, is deleted and replaced with two amino acids to give a GyrB27-A56(GKdel/Tyr123Phe) construct, crystal structure with bound gyrase. The recombinant construct improves the resolution of the crystal in X-ray diffraction, overview
additional information
the small, flexible Greek key or tail domain, residues 544-579, in the GyrB subunit, which does not make contact with the DNA in the crystal structure at 3.5 A resolution, is deleted and replaced with two amino acids to give a GyrB27-A56(GKdel/Tyr123Phe) construct, crystal structure with bound gyrase. The recombinant construct improves the resolution of the crystal in X-ray diffraction, overview
additional information
-
the small, flexible Greek key or tail domain, residues 544-579, in the GyrB subunit, which does not make contact with the DNA in the crystal structure at 3.5 A resolution, is deleted and replaced with two amino acids to give a GyrB27-A56(GKdel/Tyr123Phe) construct, crystal structure with bound gyrase. The recombinant construct improves the resolution of the crystal in X-ray diffraction, overview
additional information
the small, flexible Greek key or tail domain, residues 544-579, in the GyrB subunit, which does not make contact with the DNA in the crystal structure at 3.5 A resolution, is deleted and replaced with two amino acids to give a GyrB27-A56(GKdel/Tyr123Phe) construct, crystal structure with bound gyrase. The recombinant construct improves the resolution of the crystal in X-ray diffraction, overview
additional information
the small, flexible Greek key or tail domain, residues 544-579, in the GyrB subunit, which does not make contact with the DNA in the crystal structure at 3.5 A resolution, is deleted and replaced with two amino acids to give a GyrB27-A56(GKdel/Tyr123Phe) construct, crystal structure with bound gyrase. The recombinant construct improves the resolution of the crystal in X-ray diffraction, overview
additional information
-
the small, flexible Greek key or tail domain, residues 544-579, in the GyrB subunit, which does not make contact with the DNA in the crystal structure at 3.5 A resolution, is deleted and replaced with two amino acids to give a GyrB27-A56(GKdel/Tyr123Phe) construct, crystal structure with bound gyrase. The recombinant construct improves the resolution of the crystal in X-ray diffraction, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant DNA gyrase construct GyrB27-A56(GKdel/Tyr123Phe) from Escherichia coli by a method involving gel filtration
recombinant DNA gyrase construct GyrB27-A56(GKdel/Tyr123Phe) from Escherichia coli by a method involving gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of the DNA gyrase construct GyrB27-A56(GKdel/Tyr123Phe) in Escherichia coli
expression of the DNA gyrase construct GyrB27-A56(GKdel/Tyr123Phe) in Escherichia coli
Protein expression performed in Escherichia coli B834 DE3 (plysS)
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pharmacology
Topo II are attractive targets for design of antitumor agents
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sutcliffe, J.A.; Gootz, T.D.; Barrett, J.F.
Biochemical characteristics and physiological significance of major DNA topoisomerases
Antimicrob. Agents Chemother.
33
2027-2033
1989
Bacillus subtilis, Bacteria, Citrobacter freundii, Drosophila melanogaster, Escherichia coli, eukaryota, Micrococcus luteus, Staphylococcus aureus, Pseudomonas aeruginosa, Streptomyces niveus
Flamm, R.K.; Vojtko, C.; Chu, D.T.; Li, Q.; Beyer, J.; Hensey, D.; Ramer, N.; Clement, J.J.; Tanaka, S.K.
In vitro evaluation of ABT-719, a novel DNA gyrase inhibitor
Antimicrob. Agents Chemother.
39
964-970
1995
Acinetobacter calcoaceticus, Bacteroides thetaiotaomicron, Bacteroides fragilis, Moraxella catarrhalis, Citrobacter freundii, Clostridioides difficile, Clostridium perfringens, Corynebacterium sp., Streptococcus pneumoniae, Escherichia coli, Enterococcus faecium, Haemophilus influenzae, Klebsiella sp., Listeria monocytogenes, Staphylococcus aureus, Morganella morganii, Mycobacterium avium, Neisseria gonorrhoeae, Proteus mirabilis, Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa, Salmonella sp., Serratia marcescens, Shigella sp., Staphylococcus epidermidis, Streptococcus agalactiae, Streptococcus pyogenes, Enterococcus sp., Streptococcus viridans, Citrobacter spp., Legionella sp., Prevotella bivia, Peptostreptococcus sp., Staphylococcus aureus CiproS, Pseudomonas aeruginosa AC1679-1682
Carr, S.B.; Makris, G.; Phillips, S.E.; Thomas, C.D.
Crystallization and preliminary X-ray diffraction analysis of two N-terminal fragments of the DNA-cleavage domain of topoisomerase IV from Staphylococcus aureus
Acta Crystallogr. Sect. F
62
1164-1167
2006
Staphylococcus aureus (Q6G9K4), Staphylococcus aureus
Hassan, G.S.; Farag, N.A.; Hegazy, G.H.; Arafa, R.K.
Design and synthesis of novel benzopyran-2-one derivatives of expected antimicrobial activity through DNA gyrase-B inhibition
Arch. Pharm.
341
725-733
2008
Bacillus subtilis, Candida albicans, Micrococcus luteus, Staphylococcus aureus, Escherichia coli (P0AES6)
Bax, B.D.; Chan, P.F.; Eggleston, D.S.; Fosberry, A.; Gentry, D.R.; Gorrec, F.; Giordano, I.; Hann, M.M.; Hennessy, A.; Hibbs, M.; Huang, J.; Jones, E.; Jones, J.; Brown, K.K.; Lewis, C.J.; May, E.W.; Saunders, M.R.; Singh, O.; Spitzfaden, C.E.; Shen, C.; Shillings, A.; Theobald, A.J.; Wohlkonig, A.; Pearson, N.D.
Type IIA topoisomerase inhibition by a new class of antibacterial agents
Nature
466
935-940
2010
Staphylococcus aureus (P66937), Staphylococcus aureus (Q99XG5), Staphylococcus aureus
Werner, M.M.; Patel, B.A.; Talele, T.T.; Ashby, C.R.; Li, Z.; Zauhar, R.J.
Dual inhibition of Staphylococcus aureus DNA gyrase and topoisomerase IV activity by phenylalanine-derived (Z)-5-arylmethylidene rhodanines
Bioorg. Med. Chem.
23
6125-6137
2015
Staphylococcus aureus, Staphylococcus aureus (P0A0K8)
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