| Literature References | 1. TSAI-PFLUGFELDER, M., LIU, L.F., LIU, A.A., TEWEY, K.M., WHANG-PENG, J.,
KNUTSEN, T., HUEBNER, K., CRUCE, C.M. AND WANG, J.C.
Cloning and sequencing of cDNA encoding human DNA topoisomerase II and
localization of the gene to chromosome region 17q21-22.
PROC.NATL.ACAD.SCI.U.S.A. 85 7177-7181 (1988).
2. HINDS, M., DEISSEROTH, K., MAYES, J., ALTSCHULER, E., JANSEN, R.,
LEDLEY, F.D. AND ZWELLING, L.A.
Identification of a point mutation in the topoisomerase II gene from a
human leukemia cell line containing an amscarine-resistant form of
topoisomerase II.
CANCER RES. 51 4729-4731 (1991).
3. WIGLEY, D.B., DAVIES, G.J., DODSON, E.J., MAXWELL, A. AND DODSON, G.
Crystal structure of an N-terminal fragment of the DNA gyrase B protein.
NATURE 351 624-629 (1991).
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| Documentation | Topoisomerases catalyse the interconversion of topological isomers of DNA
and play a key role in DNA metabolism [1]. Topoisomerase I catalyses an ATP-
independent reaction, while topoisomerase II catalyses an ATP-dependent
reaction, resulting in the formation of DNA supercoils [1-3]. The supercoil
is formed by transient cleavage in both strands of double-stranded DNA,
followed by the passage of a segment of DNA through the break, and break
ligation [3]. Eukaryotic enzymes can form both positive and negative
supercoils, while prokaryotic enzymes form only negative supercoils.
Eukaryotic topoisomerase II exists as a homodimer; in bacteriophage T4 it
consists of 3 heterologous subunits; in prokaryotes it exists as a tetramer
of 2 subunits (2 each of gyrA and gyrB); and in E.coli, a second type II
topoisomerase, involved in chromosome segregation (topoisomerase IV),
consists of 2 subunits (parC and parE). GyrB, parE, and the product of
bacteriophage T4 gene 39, are all similar to the eukaryotic proteins [1-3].
Structural studies of E.coli topoisomerase II have shown that the enzyme
binds to DNA, forming a complex in which a DNA strand of approximately 120
base pairs is wound around a protein core [3]. At low resolution, this
complex resembles a flattened sphere, and may be heart-shaped, with the DNA
embedded in the protein. There is evidence for channels or cavities in
the complex, which may have a role in the DNA translocation process [3].
The gyrB protein possesses 2 uniquely-folded domains. The N-terminal domain
(domain 1) possesses ATP-binding and hydrolysis functions, and forms an
8-stranded anti-parallel beta-sheet with unusual strand connectivities - the
structure, which is stabilised by a hydrophobic core, can be subdivided
into 6- and 2-stranded anti-parallel sheets, connected by a parallel sheet
[3]. The C-terminal domain (domain 2) contains a 4-stranded mixed parallel
and anti-parallel beta-sheet. Four helices are also present, 2 of which are
rich in arginine residues. The gyrB dimer is punctured by a 20A hole, which
may provide a gateway through which DNA is passed during supercoiling [3].
Every arginine of domain 2 protrudes into this hole, possibly creating a
DNA-binding surface [3].
From this structural information and results of various biochemical studies,
a possible mechanism has been proposed: DNA is first bound by the gyrB
dimer, then cleaved by gyrA. A large conformational change allows passage
of another DNA strand through the double-stranded break and into the protein
complex. This may involve ATP binding, exploiting the energy of association
of ATP to the complex to stabilise an unfavourable protein conformation.
The DNA break is then repaired by ligation, and the whole DNA molecule
released - this possibly involves hydrolysis of ATP to ADP and organic
phosphorous, which can dissociate from the protein, allowing the protein
complex to return to its favoured conformation, and releasing the DNA [3].
TPI2FAMILY is a 9-element fingerprint that provides a signature for the type
II DNA topoisomerase family. The fingerprint was derived from an initial
alignment of 8 sequences: the motifs were drawn from conserved regions
spanning virtually the full length of the gyrB domain - motif 5 includes the
region encoded by PROSITE pattern TOPOISOMERASE_II (PS0177), which contains
a well-conserved pentapeptide. Two iterations on OWL26.3 were required to
reach convergence, at which point a true set comprising 47 sequences was
identified. Fifteen partial matches were also found, all of which were
topoisomerase II fragments.
An update on SPTR37_9f identified a true set of 82 sequences, and 7
partial matches.
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| Sequence Titles | GYBR_STRSH DNA GYRASE SUBUNIT B, NOVOBIOCIN-RESISTANT (EC 5.99.1.3) - STREPTOMYCES SPHAEROIDES.
GYBS_STRSH DNA GYRASE SUBUNIT B, NOVOBIOCIN-SENSITIVE (EC 5.99.1.3) - STREPTOMYCES SPHAEROIDES.
GYRB_AQUAE DNA GYRASE SUBUNIT B (EC 5.99.1.3) - AQUIFEX AEOLICUS.
GYRB_BACS5 DNA GYRASE SUBUNIT B (EC 5.99.1.3) - BACILLUS HALODURANS (BACILLUS SP. (STRAIN C-125)).
GYRB_BACSU DNA GYRASE SUBUNIT B (EC 5.99.1.3) - BACILLUS SUBTILIS.
GYRB_BARBA DNA GYRASE SUBUNIT B (EC 5.99.1.3) - BARTONELLA BACILLIFORMIS.
GYRB_BORBU DNA GYRASE SUBUNIT B (EC 5.99.1.3) - BORRELIA BURGDORFERI (LYME DISEASE SPIROCHETE).
GYRB_BUCAP DNA GYRASE SUBUNIT B (EC 5.99.1.3) - BUCHNERA APHIDICOLA.
GYRB_CLOAB DNA GYRASE SUBUNIT B (EC 5.99.1.3) - CLOSTRIDIUM ACETOBUTYLICUM.
GYRB_ECOLI DNA GYRASE SUBUNIT B (EC 5.99.1.3) - ESCHERICHIA COLI.
GYRB_HAEIN DNA GYRASE SUBUNIT B (EC 5.99.1.3) - HAEMOPHILUS INFLUENZAE.
GYRB_HALSQ DNA GYRASE SUBUNIT B (EC 5.99.1.3) - HALOFERAX SP. (STRAIN AA 2.2).
GYRB_HELPY DNA GYRASE SUBUNIT B (EC 5.99.1.3) - HELICOBACTER PYLORI (CAMPYLOBACTER PYLORI).
GYRB_MYCCA DNA GYRASE SUBUNIT B (EC 5.99.1.3) - MYCOPLASMA CAPRICOLUM.
GYRB_MYCGA DNA GYRASE SUBUNIT B (EC 5.99.1.3) - MYCOPLASMA GALLISEPTICUM.
GYRB_MYCGE DNA GYRASE SUBUNIT B (EC 5.99.1.3) - MYCOPLASMA GENITALIUM.
GYRB_MYCHO DNA GYRASE SUBUNIT B (EC 5.99.1.3) - MYCOPLASMA HOMINIS.
GYRB_MYCLE DNA GYRASE SUBUNIT B (EC 5.99.1.3) - MYCOBACTERIUM LEPRAE.
GYRB_MYCPN DNA GYRASE SUBUNIT B (EC 5.99.1.3) - MYCOPLASMA PNEUMONIAE.
GYRB_MYCSM DNA GYRASE SUBUNIT B (EC 5.99.1.3) - MYCOBACTERIUM SMEGMATIS.
GYRB_MYCTU DNA GYRASE SUBUNIT B (EC 5.99.1.3) - MYCOBACTERIUM TUBERCULOSIS.
GYRB_NEIGO DNA GYRASE SUBUNIT B (EC 5.99.1.3) - NEISSERIA GONORRHOEAE.
GYRB_PSEPU DNA GYRASE SUBUNIT B (EC 5.99.1.3) - PSEUDOMONAS PUTIDA.
GYRB_SALTY DNA GYRASE SUBUNIT B (EC 5.99.1.3) - SALMONELLA TYPHIMURIUM.
GYRB_SPICI DNA GYRASE SUBUNIT B (EC 5.99.1.3) - SPIROPLASMA CITRI.
GYRB_STAAU DNA GYRASE SUBUNIT B (EC 5.99.1.3) - STAPHYLOCOCCUS AUREUS.
GYRB_STRCO DNA GYRASE SUBUNIT B (EC 5.99.1.3) - STREPTOMYCES COELICOLOR.
GYRB_STRPN DNA GYRASE SUBUNIT B (EC 5.99.1.3) - STREPTOCOCCUS PNEUMONIAE.
GYRB_SYNY3 DNA GYRASE SUBUNIT B (EC 5.99.1.3) - SYNECHOCYSTIS SP. (STRAIN PCC 6803).
GYRB_TREDE DNA GYRASE SUBUNIT B - TREPONEMA DENTICOLA.
GYRB_TREPA DNA GYRASE SUBUNIT B (EC 5.99.1.3) - TREPONEMA PALLIDUM.
O41065 PBCV-1 DNA TOPOISOMERASE II - PARAMECIUM BURSARIA CHLORELLA VIRUS 1 (PBCV-1).
O55078 DNA TOPOISOMERASE II ALPHA (EC 5.99.1.3) - CRICETULUS LONGICAUDATUS (LONG-TAILED HAMSTER) (CHINESE HAMSTER).
O55079 DNA TOPOISOMERASE II ALPHA (EC 5.99.1.3) - CRICETULUS LONGICAUDATUS (LONG-TAILED HAMSTER) (CHINESE HAMSTER).
O59864 TYPEII DNA TOPOISOMERASE - EMERICELLA NIDULANS (ASPERGILLUS NIDULANS).
O62199 F32A11.4 PROTEIN - CAENORHABDITIS ELEGANS.
O68071 DNA GYRASE SUBUNIT B (EC 5.99.1.3) - RHODOBACTER CAPSULATUS (RHODOPSEUDOMONAS CAPSULATA).
O69998 PUTATIVE DNA GYRASE SUBUNIT B - STREPTOMYCES COELICOLOR.
O74336 DNA TOPOISOMERASE II - SCHIZOSACCHAROMYCES POMBE (FISSION YEAST).
O84193 DNA GYRASE SUBUNIT B - CHLAMYDIA TRACHOMATIS.
O84668 DNA GYRASE SUBUNIT B - CHLAMYDIA TRACHOMATIS.
O86093 DNA GYRASE B SUBUNIT - METHYLOVORUS SP. STRAIN SS1.
P77993 DNA TOPOISOMERASE II SUBUNIT B - THERMOTOGA MARITIMA.
P95681 DNA TOPOISOMERASE IV GRLB SUBUNIT - STAPHYLOCOCCUS AUREUS.
PARE_BACSU TOPOISOMERASE IV SUBUNIT B (EC 5.99.1.-) - BACILLUS SUBTILIS.
PARE_BORBU TOPOISOMERASE IV SUBUNIT B (EC 5.99.1.-) - BORRELIA BURGDORFERI (LYME DISEASE SPIROCHETE).
PARE_CAUCR TOPOISOMERASE IV SUBUNIT B (EC 5.99.1.-) - CAULOBACTER CRESCENTUS.
PARE_ECOLI TOPOISOMERASE IV SUBUNIT B (EC 5.99.1.-) - ESCHERICHIA COLI.
PARE_HAEIN TOPOISOMERASE IV SUBUNIT B (EC 5.99.1.-) - HAEMOPHILUS INFLUENZAE.
PARE_MYCGE TOPOISOMERASE IV SUBUNIT B (EC 5.99.1.-) - MYCOPLASMA GENITALIUM.
PARE_MYCPN TOPOISOMERASE IV SUBUNIT B (EC 5.99.1.-) - MYCOPLASMA PNEUMONIAE.
PARE_SALTY TOPOISOMERASE IV SUBUNIT B (EC 5.99.1.-) - SALMONELLA TYPHIMURIUM.
PARE_STAAU TOPOISOMERASE IV SUBUNIT B (EC 5.99.1.-) - STAPHYLOCOCCUS AUREUS.
PARE_STRPN TOPOISOMERASE IV SUBUNIT B (EC 5.99.1.-) - STREPTOCOCCUS PNEUMONIAE.
Q59526 TOPOISOMERASE II SUBUNIT B (EC 5.99.1.3) - MYCOPLASMA GALLISEPTICUM.
Q59957 DNA GYRASE - STREPTOCOCCUS PNEUMONIAE.
TOP2_ARATH DNA TOPOISOMERASE II (EC 5.99.1.3) - ARABIDOPSIS THALIANA (MOUSE-EAR CRESS).
TOP2_ASFB7 DNA TOPOISOMERASE II (EC 5.99.1.3) - AFRICAN SWINE FEVER VIRUS (STRAIN BA71V) (ASFV).
TOP2_ASFM2 DNA TOPOISOMERASE II (EC 5.99.1.3) - AFRICAN SWINE FEVER VIRUS (ISOLATE MALAWI LIL 20/1) (ASFV).
TOP2_BOMMO DNA TOPOISOMERASE II (EC 5.99.1.3) (TOPOII) - BOMBYX MORI (SILK MOTH).
TOP2_CAEEL PROBABLE DNA TOPOISOMERASE II (EC 5.99.1.3) - CAENORHABDITIS ELEGANS.
TOP2_CANAL DNA TOPOISOMERASE II (EC 5.99.1.3) - CANDIDA ALBICANS (YEAST).
TOP2_CRIFA DNA TOPOISOMERASE II (EC 5.99.1.3) - CRITHIDIA FASCICULATA.
TOP2_DROME DNA TOPOISOMERASE II (EC 5.99.1.3) - DROSOPHILA MELANOGASTER (FRUIT FLY).
TOP2_PEA DNA TOPOISOMERASE II (EC 5.99.1.3) - PISUM SATIVUM (GARDEN PEA).
TOP2_PLAFK DNA TOPOISOMERASE II (EC 5.99.1.3) - PLASMODIUM FALCIPARUM (ISOLATE K1 / THAILAND).
TOP2_SCHPO DNA TOPOISOMERASE II (EC 5.99.1.3) - SCHIZOSACCHAROMYCES POMBE (FISSION YEAST).
TOP2_TRYBB DNA TOPOISOMERASE II (EC 5.99.1.3) - TRYPANOSOMA BRUCEI BRUCEI.
TOP2_TRYCR DNA TOPOISOMERASE II (EC 5.99.1.3) - TRYPANOSOMA CRUZI.
TOP2_YEAST DNA TOPOISOMERASE II (EC 5.99.1.3) - SACCHAROMYCES CEREVISIAE (BAKER'S YEAST).
TP2A_CHICK DNA TOPOISOMERASE II, ALPHA ISOZYME (EC 5.99.1.3) - GALLUS GALLUS (CHICKEN).
TP2A_CRIGR DNA TOPOISOMERASE II, ALPHA ISOZYME (EC 5.99.1.3) - CRICETULUS GRISEUS (CHINESE HAMSTER).
TP2A_HUMAN DNA TOPOISOMERASE II, ALPHA ISOZYME (EC 5.99.1.3) - HOMO SAPIENS (HUMAN).
TP2A_MOUSE DNA TOPOISOMERASE II, ALPHA (EC 5.99.1.3) - MUS MUSCULUS (MOUSE).
TP2A_PIG DNA TOPOISOMERASE II, ALPHA (EC 5.99.1.3) - SUS SCROFA (PIG).
TP2A_RAT DNA TOPOISOMERASE II, ALPHA (EC 5.99.1.3) - RATTUS NORVEGICUS (RAT).
TP2B_CHICK DNA TOPOISOMERASE II, BETA ISOZYME (EC 5.99.1.3) - GALLUS GALLUS (CHICKEN).
TP2B_CRILO DNA TOPOISOMERASE II, BETA ISOZYME (EC 5.99.1.3) - CRICETULUS LONGICAUDATUS (LONG-TAILED HAMSTER) (CHINESE HAMSTER).
TP2B_HUMAN DNA TOPOISOMERASE II, BETA ISOZYME (EC 5.99.1.3) - HOMO SAPIENS (HUMAN).
TP2B_MOUSE DNA TOPOISOMERASE II, BETA ISOZYME (EC 5.99.1.3) - MUS MUSCULUS (MOUSE).
TP2M_CAEEL PUTATIVE DNA TOPOISOMERASE II, MITOCHONDRIAL PRECURSOR (EC 5.99.1.3) - CAENORHABDITIS ELEGANS.
TP2M_DICDI DNA TOPOISOMERASE II, MITOCHONDRIAL PRECURSOR (EC 5.99.1.3) - DICTYOSTELIUM DISCOIDEUM (SLIME MOLD).
GYRB_MYXXA DNA GYRASE SUBUNIT B (EC 5.99.1.3) - MYXOCOCCUS XANTHUS.
O29720 DNA GYRASE, SUBUNIT B (GYRB) - ARCHAEOGLOBUS FULGIDUS.
Q27537 SIMILARITY TO DNA TOPOISOMERASE II - CAENORHABDITIS ELEGANS.
TOPL_BPT4 DNA TOPOISOMERASE LARGE SUBUNIT (EC 5.99.1.3) (PROTEIN GP39) - BACTERIOPHAGE T4.
TOPS_BPT4 DNA TOPOISOMERASE SMALL SUBUNIT (EC 5.99.1.3) (PROTEIN GP60) - BACTERIOPHAGE T4.
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