DNA topoisomerase activity
Definition
Target type: molecularfunction
Catalysis of the transient cleavage and passage of individual DNA strands or double helices through one another, resulting a topological transformation in double-stranded DNA. [GOC:mah, PMID:8811192]
DNA topoisomerases are enzymes that catalyze the controlled breakage and rejoining of DNA strands. Their primary function is to regulate the topological state of DNA, which is essential for many crucial cellular processes, including DNA replication, transcription, and chromosome segregation. DNA topoisomerases work by introducing transient breaks in the DNA backbone, allowing the DNA strands to rotate around each other, and then resealing the breaks. This process changes the linking number of the DNA, which is a measure of the number of times one DNA strand winds around the other. There are two main types of DNA topoisomerases: type I and type II. Type I topoisomerases introduce a single-strand break in the DNA, while type II topoisomerases introduce a double-strand break. Type I topoisomerases relieve torsional stress in the DNA, which can arise during DNA replication or transcription. Type II topoisomerases are involved in more complex topological changes, such as untangling DNA strands, separating DNA molecules, and resolving catenanes (interlocked DNA circles). The catalytic cycle of DNA topoisomerases involves several steps: 1) DNA binding: The topoisomerase recognizes and binds to the DNA substrate. 2) DNA cleavage: The topoisomerase introduces a transient break in the DNA backbone. 3) Strand passage: The cleaved DNA strand is passed through the break, changing the topology of the DNA. 4) DNA religation: The topoisomerase reseals the DNA break, restoring the integrity of the DNA molecule. DNA topoisomerases are essential for life and are highly conserved across all domains of life. Dysregulation of DNA topoisomerase activity can lead to various human diseases, including cancer, developmental defects, and neurodegenerative disorders. Many anticancer drugs target DNA topoisomerases, inhibiting their activity and leading to DNA damage and cell death.'
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Proteins (5)
| Protein | Definition | Taxonomy |
|---|---|---|
| DNA topoisomerase 4 subunit B | A DNA topoisomerase 4 subunit B that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P20083] | Escherichia coli K-12 |
| DNA topoisomerase 4 subunit A | A DNA topoisomerase 4 subunit A that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P0AFI2] | Escherichia coli K-12 |
| DNA topoisomerase 4 subunit A | A DNA topoisomerase 4 subunit A that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P0AFI2] | Escherichia coli K-12 |
| DNA gyrase subunit B | A DNA gyrase subunit B that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P0AES6] | Escherichia coli K-12 |
| DNA gyrase subunit A | A DNA gyrase subunit A that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P0AES4] | Escherichia coli K-12 |
Compounds (18)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| ciprofloxacin | ciprofloxacin : A quinolone that is quinolin-4(1H)-one bearing cyclopropyl, carboxylic acid, fluoro and piperazin-1-yl substituents at positions 1, 3, 6 and 7, respectively. Ciprofloxacin: A broad-spectrum antimicrobial carboxyfluoroquinoline. | aminoquinoline; cyclopropanes; fluoroquinolone antibiotic; N-arylpiperazine; quinolinemonocarboxylic acid; quinolone; quinolone antibiotic; zwitterion | antibacterial drug; antiinfective agent; antimicrobial agent; DNA synthesis inhibitor; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; environmental contaminant; topoisomerase IV inhibitor; xenobiotic |
| enoxacin | enoxacin : A 1,8-naphthyridine derivative that is 1,4-dihydro-1,8-naphthyridine with an ethyl group at the 1 position, a carboxy group at the 3-position, an oxo sustituent at the 4-position, a fluoro substituent at the 5-position and a piperazin-1-yl group at the 7 position. An antibacterial, it is used in the treatment of urinary-tract infections and gonorrhoea. Enoxacin: A broad-spectrum 6-fluoronaphthyridinone antibacterial agent that is structurally related to NALIDIXIC ACID. | 1,8-naphthyridine derivative; amino acid; fluoroquinolone antibiotic; monocarboxylic acid; N-arylpiperazine; quinolone antibiotic | antibacterial drug; DNA synthesis inhibitor |
| isoniazid | Hydra: A genus of freshwater polyps in the family Hydridae, order Hydroida, class HYDROZOA. They are of special interest because of their complex organization and because their adult organization corresponds roughly to the gastrula of higher animals. hydrazide : Compounds derived from oxoacids RkE(=O)l(OH)m (l =/= 0) by replacing -OH by -NRNR2 (R groups are commonly H). (IUPAC). | carbohydrazide | antitubercular agent; drug allergen |
| nalidixic acid | 1,8-naphthyridine derivative; monocarboxylic acid; quinolone antibiotic | antibacterial drug; antimicrobial agent; DNA synthesis inhibitor | |
| norfloxacin | norfloxacin : A quinolinemonocarboxylic acid with broad-spectrum antibacterial activity against most gram-negative and gram-positive bacteria. Norfloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase. Norfloxacin: A synthetic fluoroquinolone (FLUOROQUINOLONES) with broad-spectrum antibacterial activity against most gram-negative and gram-positive bacteria. Norfloxacin inhibits bacterial DNA GYRASE. | fluoroquinolone antibiotic; N-arylpiperazine; quinolinemonocarboxylic acid; quinolone; quinolone antibiotic | antibacterial drug; DNA synthesis inhibitor; environmental contaminant; xenobiotic |
| ofloxacin | 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid : An oxazinoquinoline that is 2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinolin-7-one substituted by methyl, carboxy, fluoro, and 4-methylpiperazin-1-yl groups at positions 3, 6, 9, and 10, respectively. ofloxacin : A racemate comprising equimolar amounts of levofloxacin and dextrofloxacin. It is a synthetic fluoroquinolone antibacterial agent which inhibits the supercoiling activity of bacterial DNA gyrase, halting DNA replication. Ofloxacin: A synthetic fluoroquinolone antibacterial agent that inhibits the supercoiling activity of bacterial DNA GYRASE, halting DNA REPLICATION. | 3-oxo monocarboxylic acid; N-arylpiperazine; N-methylpiperazine; organofluorine compound; oxazinoquinoline | |
| gatifloxacin | gatifloxacin : A monocarboxylic acid that is 4-oxo-1,4-dihydroquinoline-3-carboxylic acid which is substituted on the nitrogen by a cyclopropyl group and at positions 6, 7, and 8 by fluoro, 3-methylpiperazin-1-yl, and methoxy groups, respectively. Gatifloxacin is an antibiotic of the fourth-generation fluoroquinolone family, that like other members of that family, inhibits the bacterial topoisomerase type-II enzymes. Gatifloxacin: A fluoroquinolone antibacterial agent and DNA TOPOISOMERASE II inhibitor that is used as an ophthalmic solution for the treatment of BACTERIAL CONJUNCTIVITIS. | N-arylpiperazine; organofluorine compound; quinolinemonocarboxylic acid; quinolone; quinolone antibiotic | antiinfective agent; antimicrobial agent; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor |
| triclosan | aromatic ether; dichlorobenzene; monochlorobenzenes; phenols | antibacterial agent; antimalarial; drug allergen; EC 1.3.1.9 [enoyl-[acyl-carrier-protein] reductase (NADH)] inhibitor; EC 1.5.1.3 (dihydrofolate reductase) inhibitor; fungicide; persistent organic pollutant; xenobiotic | |
| 4-cumylphenol | diarylmethane | ||
| 4-phenoxyphenol | phenoxyphenol | ||
| bis(4-oxyphenyl)sulfide | 4,4'-thiodiphenol: structure in first source | phenols | |
| moxifloxacin | moxifloxacin : A quinolone that consists of 4-oxo-1,4-dihydroquinoline-3-carboxylic acid bearing a cyclopropyl substituent at position 1, a fluoro substitiuent at position 6, a (4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl group at position 7 and a methoxy substituent at position 8. A member of the fluoroquinolone class of antibacterial agents. Moxifloxacin: A fluoroquinolone that acts as an inhibitor of DNA TOPOISOMERASE II and is used as a broad-spectrum antibacterial agent. | aromatic ether; cyclopropanes; fluoroquinolone antibiotic; pyrrolidinopiperidine; quinolinemonocarboxylic acid; quinolone; quinolone antibiotic | antibacterial drug |
| linezolid | acetamides; morpholines; organofluorine compound; oxazolidinone | antibacterial drug; protein synthesis inhibitor | |
| gemifloxacin | gemifloxacin : A 1,4-dihydro-1,8-naphthyridine with a carboxy group at the 3-position, an oxo sustituent at the 4-position, a fluoro substituent at the 5-position and a substituted pyrrolin-1-yl group at the 7-position. Gemifloxacin: A naphthyridine and fluoroquinolone derivative antibacterial agent and DNA TOPOISOMERASE II inhibitor that is used for the treatment of community-acquired pneumonia and acute bacterial infections associated with chronic bronchitis. | 1,8-naphthyridine derivative; fluoroquinolone antibiotic; monocarboxylic acid; quinolone antibiotic | antibacterial drug; antimicrobial agent; topoisomerase IV inhibitor |
| pd 0305970 | |||
| gsk299423 | GSK299423: structure in first source | ||
| novobiocin | novobiocin : A coumarin-derived antibiotic obtained from Streptomyces niveus. Novobiocin: An antibiotic compound derived from Streptomyces niveus. It has a chemical structure similar to coumarin. Novobiocin binds to DNA gyrase, and blocks adenosine triphosphatase (ATPase) activity. (From Reynolds, Martindale The Extra Pharmacopoeia, 30th ed, p189) | carbamate ester; ether; hexoside; hydroxycoumarin; monocarboxylic acid amide; monosaccharide derivative; phenols | antibacterial agent; antimicrobial agent; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; Escherichia coli metabolite; hepatoprotective agent |
| clorobiocin | clorobiocin: chlorine-containing antibiotic related to novobiocin |