PROSITE documentation PDOC52040 [for PROSITE entry PS52040]
Topoisomerase (Topo) IIA-type catalytic domain profile


DNA topoisomerases (Topos) are enzymes that solve topological problems associated with important processes such as DNA replication, transcription, recombination and chromatin remodeling by introducing transient single or double stranded breaks in the DNA and releasing accumulated strain. They may have appeared early during the formation of the modern DNA world. Several families and subfamilies of the two types of DNA topoisomerases (I and II) have been described in the three cellular domains of life (Archaea, Bacteria and Eukarya), as well as in viruses infecting eukaryotes or bacteria. The main families of DNA topoisomerases, Topo IA, Topo IB, Topo IC (Topo V), Topo IIA and Topo IIB (Topo VI) are not homologous, indicating that they originated independently. However, some of them share homologous modules or subunits that were probably recruited independently to produce different topoisomerase activities [1,2,3,4,5,6].

Type II DNA topoisomerases introduce double-strand breaks in a DNA duplex and force the passage of another duplex through this break. The DNA cleavage, energy storage and religation reactions are chemically similar to those performed by Type I topoisomerases, with the formation of a phosphotyrosine link between DNA and the enzyme, except that the two strands of the DNA duplex are broken in a concerted reaction. In contrast to Topo I that can make transient links with either the 5' end (Topo IA) or the 3' end (Topo IB and IC) of the DNA breaks, all Topo II make transient links with the 5' end of the DNA breaks. All Type II enzymes can catenate (or decatenate) and knot (or unknot) circular duplex DNA, and alter DNA superhelicity by relaxing positively or negatively supercoiled DNA. In contrast to Topo I, all Type II topoisomerases are ATPdependent and multimeric enzymes with a dyad symmetry. Each "half-enzyme" is formed by the combination of one ATP binding domain and one catalytic breakage-reunion domain containing the active site tyrosine. Topo II are essential in all cells for segregation of the chromosomal DNA after DNA replication and before cell division. Although ubiquitous, Type II enzymes are organized into two families, Topo IIA and IIB [1,2,3,4,5,6].

Type IIA enzymes include topoisomerase II (topo II) encoded by both eukaryotes and viruses, and DNA gyrase and topoisomerase IV (topo IV) encoded by bacteria. Topo IIA are homologous at the primary sequence level although their oligomerization states are different. They all possess an ATPase domain and a DNA binding/cleavage domain. These two domains are present on the same polypeptide chain in eukaryal and eukaryotic viruses encoded Topo IIA, or present on two different polypeptide chains in bacterial enzymes or three polypeptide chains in the bacteriophage T4 encoded Topo IIA. Each domain is present in two copies in the enzyme, thus eukaryotic Topo IIA are homodimers and bacterial Topo IIA heterotetramers, while the T4 Topo IIA is a heterohexamer. The ATPase domain is located on the N-terminal region of eukaryal enzymes or on the B subunit of bacterial enzymes (GyrB or ParE for gyrase and Topo IV, respectively). The Topo IIA-type catalytic domain containing the active site tyrosine involved in the covalent complex with DNA is located on the C-terminal region of eukaryal enzymes or on the A-subunit of bacterial enzymes (GyrA or ParC for gyrase and Topo IV respectively) [1,2,3,4,5,6].

The Topo IIA-type catalytic domain contains two subdomains, termed the winged-helix domain (WHD), and the tower domain (see <PDB:8J9Y>). The WHD subdomain is a five-helix bundle bearing the strictly conserved catalytic tyrosine. The active-site tyrosines are on loops at either end of the dimer interface and sit at the ends of strongly basic grooves created by the dimer-related monomers. The tower subdomain has a compact "spire" containing two antiparallel β-strands packed against a four-helix bundle and a loose "base" consisting of mixed structural elements [1,2,3,4,5,6].

The profile we developed covers the entire Topo IIA-type catalytic domain.

Last update:

October 2023 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

TOPO_IIA, PS52040; Topoisomerase (Topo) IIA-type catalytic domain profile  (MATRIX)


1AuthorsForterre P. Gribaldo S. Gadelle D. Serre M.-C.
TitleOrigin and evolution of DNA topoisomerases.
SourceBiochimie 89:427-446(2007).
PubMed ID17293019

2AuthorsZhao Y. Kuang W. An Q. Li J. Wang Y. Deng Z.
TitleCryo-EM structures of African swine fever virus topoisomerase.
SourcemBio 0:E0122823-E0122823(2023).
PubMed ID37610250

3AuthorsBerger J.M. Gamblin S.J. Harrison S.C. Wang J.C.
TitleStructure and mechanism of DNA topoisomerase II.
SourceNature 379:225-232(1996).
PubMed ID8538787

4AuthorsBerger J.M. Wang J.C.
TitleRecent developments in DNA topoisomerase II structure and mechanism.
SourceCurr. Opin. Struct. Biol. 6:84-90(1996).
PubMed ID8696977

5AuthorsMorais Cabral J.H. Jackson A.P. Smith C.V. Shikotra N. Maxwell A. Liddington R.C.
TitleCrystal structure of the breakage-reunion domain of DNA gyrase.
SourceNature 388:903-906(1997).
PubMed ID9278055

6AuthorsSchmidt B.H. Osheroff N. Berger J.M.
TitleStructure of a topoisomerase II-DNA-nucleotide complex reveals a new control mechanism for ATPase activity.
SourceNat. Struct. Mol. Biol. 19:1147-1154(2012).
PubMed ID23022727

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