475:
Rossmann fold that contains three invariant acidic residues that coordinate magnesium ions involved in DNA cleavage and DNA religation. The structure of the Toprim fold and DNA-binding core of yeast topoisomerase II was first solved by Berger and Wang, and the first gyrase DNA-binding core was solved by Morais Cabral et al. The structure solved by Berger revealed important insights into the function of the enzyme. The DNA-binding core consists of the WHD, which leads to a tower domain. A coiled-coil region leads to a C-terminal domain that forms the main dimer interface for this crystal state (often termed the C-gate). While the original topoisomerase II structure shows a situation where the WHDs are separated by a large distance, the structure of gyrase shows a closed conformation, where the WHD close.
479:
was eventually substantiated by the Dong et al. structure that was solved in the presence of DNA. This last structure showed that the Toprim domain and the WHD formed a cleavage complex very similar to that of the type IA topoisomerases and indicated how DNA-binding and cleavage could be uncoupled, and the structure showed that DNA was bent by ~150 degrees through an invariant isoleucine (in topoisomerase II it is I833 and in gyrase it is I172). This mechanism of bending resembles closely that of integration host factor (IHF) and HU, two architectural proteins in bacteria. In addition, while the previous structures of the DNA-binding core had the C-gate closed, this structure captured the gate open, a key step in the two-gate mechanism (see below).
278:
have the special ability to relax DNA to a state below that of thermodynamic equilibrium, a feature unlike type IA, IB, and IIB topoisomerases. This ability, known as topology simplification, was first identified by
Rybenkov et al. The hydrolysis of ATP drives this simplification, but a clear molecular mechanism for this simplification is still lacking. Several models to explain this phenomenon have been proposed, including two models that rely on the ability of type IIA topoisomerases to recognize bent DNA duplexes. Biochemistry, electron microscopy, and recent structures of topoisomerase II bound to DNA reveal that type IIA topoisomerases bind at the apices of DNA, supporting this model.
579:
release of an inorganic phosphate leads to the cleavage of the G-segment, as the catalytic tyrosines form a covalent phosphotyrosine bond with the 5' end of the DNA. This creates a four-base overhang and a double-stranded break in the G-segment. As the DNA-binding gate separates, the T-segment is transferred through the G-segment. The G-segment is sealed, leading to the C-terminal gate (or C-gate) to open, allowing for the release of the T-segment. Release of product ADP leads to a reset of the system, and allows a second T-segment to be captured.
508:
375:
2902:
495:
bends DNA by wrapping the nucleic acid around itself. The bending of DNA by gyrase has been proposed as a key mechanism in the ability of gyrase to introduce negative supercoils into the DNA. This is consistent with footprinting data that shows that gyrase has a 140-base-pair footprint. Both gyrase and topoisomerase IV CTDs bend DNA, but only gyrase introduces negative supercoils.
258:. Along with gyrase, most prokaryotes also contain a second type IIA topoisomerase, termed topoisomerase IV. Gyrase and topoisomerase IV differ by their C-terminal domains, which is believed to dictate substrate specificity and functionality for these two enzymes. Footprinting indicates that gyrase, which forms a 140-base-pair footprint and wraps DNA, introduces negative
292:
719:
DNA gyrase can partially compensate for the loss of the phage T4 gene products, mutants defective in either genes 39, 52 or 60 do not completely abolish phage DNA replication, but rather delay its initiation. The rate of DNA elongation is not slower than wild-type in such mutant infections. Mutants
494:
The C-terminal region of the prokaryotic topoisomerases has been solved for multiple species. The first structure of a C-terminal domain of gyrase was solved by
Corbett et al. and the C-terminal domain of topoisomerase IV was solved by Corbett et al. The structures formed a novel beta barrel, which
277:
Type IIA topoisomerases are essential in the separation of entangled daughter strands during replication. This function is believed to be performed by topoisomerase II in eukaryotes and by topoisomerase IV in prokaryotes. Failure to separate these strands leads to cell death. Type IIA topoisomerases
561:
A recent structure of the topo VI A/B complex was solved, showing an open and closed conformation, two states that are predicted in the two-gate mechanism (see below). These structures, of which one is an X-ray crystal structure and the other is a Small-Angle X-ray
Scattering (SAXS) reconstruction,
478:
The topoisomerase II core was later solved in new conformations, including one by Fass et al. and one by Dong et al. The Fass structure shows that the Toprim domain is flexible and that this flexibility can allow the Toprim domain to coordinate with the WHD to form a competent cleavage complex. This
474:
The central core of the protein contains a Toprim fold and a DNA-binding core that contains a winged helix domain (WHD), often referred to as a CAP domain, since it was first identified to resemble the WHD of catabolite activator protein. The catalytic tyrosine lies on this WHD. The Toprim fold is a
466:
The structures of the N-terminal ATPase domain of gyrase and yeast topoisomerase II have been solved in complex with AMPPNP (an ATP analogue), showing that two ATPase domains dimerize to form a closed conformation. For gyrase, the structure has a substantial hole in the middle, which is presumed to
602:
is the process by which two circular DNA strands are linked together like chain links. This occurs after DNA replication, where two single strands are catenated and can still replicate but cannot separate into the two daughter cells. As type II topoisomerses break a double strand, they can fix this
360:
The two classes of topoisomerases possess a similar strand passage mechanism and domain structure (see below), however they also have several important differences. Type IIA topoisomerases form double-stranded breaks with four-base pair overhangs, while type IIB topoisomerases form double-stranded
470:
Linking the ATPase domain to the Toprim fold is a helical element known as the transducer domain. This domain is thought to communicate the nucleotide state of the ATPase domain to the rest of the protein. Modifications to this domain affect topoisomerase activity, and structural work done by the
578:
A strand of DNA, called the gate, or G-segment, is bound by a central DNA-binding gate (DNA-gate). A second strand of DNA, called the transport, or T-segment, is captured by the dimerization of the N-terminal ATPase domain (the ATPase-gate) when two molecules of ATP bind. Hydrolysis of ATP and
498:
Unlike the function of the C-terminal domain of prokaryotic topoisomerases, the function of the C-terminal region of eukaryotic topoisomerase II is still not clear. Studies have suggested that this region is regulated by phosphorylation and this modulates topoisomerase activity, however more
29:
621:
Small molecules that target type II topoisomerase are divided into two classes: inhibitors and poisons. Due to their frequent presence in proliferating eukaryotic cells, inhibitors of type II topoisomerases have been extensively studied and used as anti-cancer medications.
482:
More recently, several structures of the DNA-bound structure have been solved in an attempt to understand both the chemical mechanism for DNA cleavage and the structural basis for inhibition of topoisomerase by antibacterial poisons. The first complete architecture of the
463:). For gyrase, the first polypeptide is called GyrB and the second polypeptide is called GyrA. For topo IV, the first polypeptide is called ParE and the second polypeptide is called ParC. Both Pfam signatures are found in the single-chain eukayotic topoisomerase.
590:
In the strand passage mechanism, the cleavage of DNA is key to allow the T-segment to transfer through the G-segment. The mechanism of DNA cleavage by type IIA topoisomerases has recently been the focus of many biochemical and structural biology studies.
554:
The ATPase domain of topo VI B was solved in multiple nucleotide states. It closely resembles that of the GHKL domain of topo II and MutL and shows that the nucleotide state (ADP versus ATP) effects the orientation of the transducer domain ( and 1MX0).
736:
are present. Mutants defective in genes 39, 52 and 60 have reduced ability to carry out multiplicity reactivation, a form of recombinational repair that can deal with different types of DNA damage. The gyrase specified by the genome of uninfected
525:
The organization of type IIB topoisomerases are similar to that of type IIAs, except that all type IIBs have two genes and form heterotetramers. One gene, termed topo VI-B (since it resembles gyrB), contains the ATPase domain, a transducer domain
700:
The bacteriophage (phage) T4 gyrase (type II topoismerase) is a multisubunit protein consisting of the products of genes 39, 52 and probably 60. It catalyses the relaxation of negatively or positively superhelical DNA and is employed in phage
268:
The roles of type IIB topoisomerases are less understood. Unlike type IIA topoisomerases, type IIB topoisomerases cannot simplify DNA topology (see below), but they share several structural features with type IIA topoisomerases.
396:). The Toprim fold is colored cyan; the DNA is colored orange; the HTH is colored magenta; and the C-gate is colored purple. Notice that the DNA is bent by ~160 degrees through an invariant isoleucine (Ile833 in yeast).
357:, the topoisomerase IIα is highly expressed in proliferating cells. In certain cancers, such as peripheral nerve sheath tumors, high expression of its encoded protein is also associated to poor patient survival.
642:. These molecules work by inhibiting the ATPase activity by acting as noncompetitive inhibitors of ATP. This has been shown through structural studies and biochemical studies performed by the Lindsley group.
692:) that renders quinolones ineffective. Recent structural studies have led to the discovery of a compound that no longer relies on this residue and, therefore, has efficacy against drug-resistant bacteria.
341:
Type IIB topoisomerases are structurally and biochemically distinct, and comprise a single family member, topoisomerase VI (topo VI). Type IIB topoisomerases are found in archaea and some higher plants.
2108:
McCarthy D (January 1979). "Gyrase-dependent initiation of bacteriophage T4 DNA replication: interactions of
Escherichia coli gyrase with novobiocin, coumermycin and phage DNA-delay gene products".
680:
Topoisomerase poisons have been extensively used as both anticancer and antibacterial therapies. While antibacterial compounds such as ciprofloxacin target bacterial gyrase, they fail to inhibit
521:) in an orientation similar to the yeast example. Chains are colored differently. The Toprim domain lies on the top, and the ATPase domain lies on the bottom; each forms a DNA gate.
728:
suggesting that the host compensated DNA synthesis is less accurate than that directed by wild-type phage. A mutant defective in gene 39 shows increased sensitivity to inactivation by
1722:
Bergerat A, de Massy B, Gadelle D, Varoutas PC, Nicolas A, Forterre P (March 1997). "An atypical topoisomerase II from
Archaea with implications for meiotic recombination".
582:
Type IIB topoisomerases operate through a similar fashion, except that the protein forms a two-base overhang in the G-segment and the C-terminal gate is completely missing.
232:
In animals, topoisomerase II is a chemotherapy target. In prokaryotes, gyrase is an antibacterial target. Indeed, these enzymes are of interest for a wide range of effects.
575:
Type IIA topoisomerase operates through a "two-gate" mechanism (though this is a historical notation), a mechanism supported by biochemistry as well as by structural work.
603:
state (type I topoisomerases could do this only if there were already a single-strand nick), and the correct chromosome number can remain in daughter cells. Linear DNA in
2233:
McCarthy D, Minner C, Bernstein H, Bernstein C (October 1976). "DNA elongation rates and growing point distributions of wild-type phage T4 and a DNA-delay amber mutant".
166:
1937:
669:. These small molecules target the DNA-protein complex. Some of these molecules lead to increased cleavage, whereas others, such as etoposide, inhibit religation.
185:
845:
Rybenkov VV, Ullsperger C, Vologodskii AV, Cozzarelli NR (August 1997). "Simplification of DNA topology below equilibrium values by type II topoisomerases".
558:
The structure of topo VI-A was solved by
Bergerat et al. showing that the HTH and Toprim fold had a novel conformation compared with that of topo IIA.
1995:, Liu CC, Alberts BM (October 1979). "T4 DNA topoisomerase: a new ATP-dependent enzyme essential for initiation of T4 bacteriophage DNA replication".
741:
also appears to participate in recombinational repair by providing an initiation point for the reciprocal strand exchange driven by the RecA protein.
2537:
1953:"A novel DNA-dependent protein kinase inhibitor, NU7026, potentiates the cytotoxicity of topoisomerase II poisons used in the treatment of leukemia"
487:
DNA gyrase has been solved by cryo-electron microscopy at near atomic resolution. The nucleoprotein complex was captured with a long DNA duplex and
240:
Type II topoisomerases increase or decrease the linking number of a DNA loop by 2 units, and it promotes chromosome disentanglement. For example,
33:
Structure of the 42 KDa fragment of the N-terminal ATPase and transducer domains of DNA gyrase homologous to all other type IIA topoisomerases.
361:
breaks with two base overhangs. In addition, type IIA topoisomerases are able to simplify DNA topology, while type IIB topoisomerases do not.
1913:
1071:
Wigley DB, Davies GJ, Dodson EJ, Maxwell A, Dodson G (June 1991). "Crystal structure of an N-terminal fragment of the DNA gyrase B protein".
1036:
Corbett KD, Schoeffler AJ, Thomsen ND, Berger JM (August 2005). "The structural basis for substrate specificity in DNA topoisomerase IV".
1433:
Fass D, Bogden CE, Berger JM (April 1999). "Quaternary changes in topoisomerase II may direct orthogonal movement of two DNA strands".
2621:
1783:
Corbett KD, Benedetti P, Berger JM (July 2007). "Holoenzyme assembly and ATP-mediated conformational dynamics of topoisomerase VI".
1248:"Toprim--a conserved catalytic domain in type IA and II topoisomerases, DnaG-type primases, OLD family nucleases and RecR proteins"
1195:
2048:"T4 DNA-delay proteins, required for specific DNA replication, form a complex that has ATP-dependent DNA topoisomerase activity"
178:
2319:"The genetics of the Luria-Latarjet effect in bacteriophage T4: evidence for the involvement of multiple DNA repair pathways"
383:
121:
2777:
145:
2892:
2530:
1486:
Dong KC, Berger JM (December 2007). "Structural basis for gate-DNA recognition and bending by type IIA topoisomerases".
1137:"Structure of the topoisomerase II ATPase region and its mechanism of inhibition by the chemotherapeutic agent ICRF-187"
1826:
Roca J, Wang JC (May 1994). "DNA transport by a type II DNA topoisomerase: evidence in favor of a two-gate mechanism".
732:
irradiation during the stage of phage infection after initiation of DNA replication when multiple copies of the phage
254:, introduces negative supercoils and decreases the linking number by 2. Gyrase is also able to remove knots from the
507:
306:
2762:
2878:
2865:
2852:
2839:
2826:
2813:
2800:
2563:
880:
Vologodskii AV, Zhang W, Rybenkov VV, Podtelezhnikov AA, Subramanian D, Griffith JD, Cozzarelli NR (March 2001).
2772:
607:
is so long they can be thought of as being without ends; type II topoisomerases are needed for the same reason.
2726:
2669:
2554:
2509:
1305:
Berger JM, Gamblin SJ, Harrison SC, Wang JC (January 1996). "Structure and mechanism of DNA topoisomerase II".
139:
44:
1675:"Structure of the topoisomerase VI-B subunit: implications for type II topoisomerase mechanism and evolution"
2674:
2523:
616:
126:
1869:
Berger JM, Wang JC (February 1996). "Recent developments in DNA topoisomerase II structure and mechanism".
374:
218:
2505:
715:
gyrase gyrA subunit and the phage gene 39 protein shares homology with the gyr B subunit. Since the host
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114:
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2004:
1731:
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1314:
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350:
346:
222:
2731:
2409:"Formation of covalently closed heteroduplex DNA by the combined action of gyrase and RecA protein"
412:
378:
Schematic structure of gyrase, oriented upside-down compared to the other examples in this article.
142:
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2486:
2028:
1931:
1851:
1808:
1755:
1519:
1458:
1405:
1338:
1228:
1196:"Nucleotide-dependent domain movement in the ATPase domain of a human type IIA DNA topoisomerase"
1104:
1005:
976:"DNA topoisomerase VI generates ATP-dependent double-strand breaks with two-nucleotide overhangs"
639:
66:
2478:
2438:
2389:
2340:
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2250:
2215:
2166:
2125:
2087:
2020:
1974:
1919:
1909:
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1843:
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1773:
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1704:
1663:
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1026:
997:
956:
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824:
789:
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subclass), which exists in both type II topoisomerases, type IA topoisomerases, and bacterial
388:
133:
684:
type IIA topoisomerases. In addition, drug-resistant bacteria often have a point mutation in
229:
of circular DNA by ±2. Topoisomerases are ubiquitous enzymes, found in all living organisms.
2710:
2705:
2679:
2607:
2586:
2470:
2428:
2420:
2379:
2371:
2330:
2289:
2281:
2242:
2205:
2197:
2156:
2145:"The 52-protein subunit of T4 DNA topoisomerase is homologous to the gyrA-protein of gyrase"
2117:
2077:
2067:
2012:
1964:
1878:
1835:
1792:
1739:
1694:
1686:
1635:
1625:
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1503:
1442:
1387:
1366:
Morais Cabral JH, Jackson AP, Smith CV, Shikotra N, Maxwell A, Liddington RC (August 1997).
1322:
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1045:
987:
948:
911:
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854:
816:
779:
771:
707:
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1951:
Willmore E, de Caux S, Sunter NJ, Tilby MJ, Jackson GH, Austin CA, Durkacz BW (June 2004).
2757:
2741:
2654:
702:
102:
471:
Verdine group shows that the ATP state affects the orientation of the transducer domain.
2063:
2008:
1735:
1621:
1554:
1499:
1383:
1318:
1152:
1084:
897:
305:
Please expand the section to include this information. Further details may exist on the
78:
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2384:
2359:
1571:
1538:
784:
759:
226:
206:
161:
49:
2461:
Wang JC (June 2002). "Cellular roles of DNA topoisomerases: a molecular perspective".
2433:
2408:
2294:
2269:
2210:
2185:
2161:
2144:
2082:
2047:
1882:
1699:
1674:
1640:
1605:
1272:
1247:
1171:
1136:
677:(4'-(9'-acridinylamino)methanesulfon-m-anisidide) also inhibits type 2 topoisomerase.
265:
Eukaryotic type II topoisomerase cannot introduce supercoils; it can only relax them.
2916:
2700:
2659:
2550:
2515:
2490:
2246:
2121:
1839:
916:
881:
662:
416:
1855:
1232:
1009:
548:
541:
530:
460:
453:
2649:
2186:"Nucleotide sequence of a type II DNA topoisomerase gene. Bacteriophage T4 gene 39"
2032:
1812:
1759:
1523:
1409:
1342:
1108:
430:
a central DNA-binding core (which structurally forms a heart-shaped structure), and
262:, while topoisomerase IV, which forms a 28-base-pair footprint, does not wrap DNA.
2285:
1462:
338:(topo IV). These enzymes span all domains of life and are essential for function.
2375:
858:
2873:
2808:
2644:
729:
646:
534:
488:
405:
386:
Structure of yeast topoisomerase II bound to a doubly nicked 34-mer duplex DNA (
2901:
2052:
Proceedings of the
National Academy of Sciences of the United States of America
1969:
1952:
1610:
Proceedings of the
National Academy of Sciences of the United States of America
1606:"The C-terminal domain of DNA gyrase A adopts a DNA-bending beta-pinwheel fold"
1562:
1141:
Proceedings of the
National Academy of Sciences of the United States of America
886:
Proceedings of the
National Academy of Sciences of the United States of America
2581:
2335:
2318:
1049:
952:
820:
733:
681:
666:
658:
654:
604:
599:
449:). Prokaryotes have the ATPase domain and the Toprim fold on one polypeptide (
331:
255:
251:
241:
2201:
1923:
1263:
2847:
2821:
2546:
1992:
1630:
1539:"Cryo-EM structure of the complete E. coli DNA gyrase nucleoprotein complex"
1161:
650:
259:
214:
2482:
2072:
1978:
1804:
1708:
1690:
1649:
1580:
1515:
1454:
1224:
1215:
1180:
1057:
1001:
992:
975:
925:
906:
793:
291:
2442:
2393:
2344:
2303:
2219:
2170:
1890:
1847:
1751:
1401:
1334:
1281:
1100:
960:
939:
Reece RJ, Maxwell A (January 1991). "DNA gyrase: structure and function".
866:
828:
2254:
2129:
2091:
2024:
775:
760:"The DNA cleavage reaction of topoisomerase II: wolf in sheep's clothing"
725:
635:
456:), while the DNA cleavage core and the CTD lies on a second polypeptide (
209:
that cut both strands of the DNA helix simultaneously in order to manage
1507:
974:
Buhler C, Lebbink JH, Bocs C, Ladenstein R, Forterre P (October 2001).
420:
345:
Some organisms including humans have two isoforms of topoisomerase II:
246:
109:
90:
1777:
1667:
1598:
1480:
1427:
1360:
1299:
1129:
1030:
517:
392:
326:
There are two subclasses of type II topoisomerases, type IIA and IIB.
2860:
2630:
2016:
1796:
1743:
1326:
1092:
685:
674:
627:
354:
173:
85:
73:
61:
2360:"Topoisomerase involvement in multiplicity reactivation of phage T4"
882:"Mechanism of topology simplification by type II DNA topoisomerases"
2474:
711:
bacterial host. The phage gene 52 protein shares homology with the
2834:
1392:
1367:
807:
Reece RJ, Maxwell A (1991). "DNA gyrase: structure and function".
506:
441:), while prokaryotic type II topoisomerases are heterotetramers (A
381:
373:
1446:
1368:"Crystal structure of the breakage-reunion domain of DNA gyrase"
545:
538:
527:
457:
450:
424:
97:
2603:
2519:
382:
285:
210:
28:
1194:
Wei H, Ruthenburg AJ, Bechis SK, Verdine GL (November 2005).
2358:
Miskimins R, Schneider S, Johns V, Bernstein H (June 1982).
1537:
Vanden Broeck A, Lotz C, Ortiz J, Lamour V (October 2019).
2599:
562:
show that the ATPase domain can be either open or closed.
400:
Type IIA topoisomerases consist of several key motifs:
334:, eukaryotic topoisomerase II (topo II), and bacterial
941:
Critical Reviews in Biochemistry and Molecular Biology
809:
Critical Reviews in Biochemistry and Molecular Biology
2890:
1604:
Corbett KD, Shultzaberger RK, Berger JM (May 2004).
724:
as well as increased base-substitution and deletion
2786:
2750:
2719:
2688:
2637:
2562:
437:
Eukaryotic type II topoisomerases are homodimers (A
184:
172:
160:
155:
132:
120:
108:
96:
84:
72:
60:
55:
43:
38:
21:
1246:Aravind L, Leipe DD, Koonin EV (September 1998).
1135:Classen S, Olland S, Berger JM (September 2003).
2103:
2101:
840:
838:
720:defective in genes 39, 52 or 60 show increased
499:research needs to be done to investigate this.
1120:
1118:
1021:
1019:
2615:
2531:
2046:Stetler GL, King GJ, Huang WM (August 1979).
491:, a novel bacterial topoisomerase inhibitor.
8:
626:Inhibitors of type II topoisomerase include
330:Type IIA topoisomerases include the enzymes
225:. In this process, these enzymes change the
2270:"The DNA-delay mutants of bacteriophage T4"
551:), contains the WHD and the Toprim domain.
2622:
2608:
2600:
2538:
2524:
2516:
1936:: CS1 maint: location missing publisher (
645:Poisons of type II topoisomerases include
152:
2508:at the U.S. National Library of Medicine
2432:
2383:
2334:
2293:
2209:
2160:
2081:
2071:
1968:
1785:Nature Structural & Molecular Biology
1698:
1639:
1629:
1570:
1391:
1271:
1214:
1170:
1160:
991:
915:
905:
783:
758:Deweese JE, Osheroff N (February 2009).
2897:
750:
544:). The second gene, termed topo VI-A (
2463:Nature Reviews. Molecular Cell Biology
1929:
1673:Corbett KD, Berger JM (January 2003).
244:, a type II topoisomerase observed in
22:DNA Topoisomerase II (ATP-hydrolyzing)
18:
2268:Mufti S, Bernstein H (October 1974).
1871:Current Opinion in Structural Biology
7:
1203:The Journal of Biological Chemistry
980:The Journal of Biological Chemistry
408:(for gyrase, Hsp, kinase and MutL),
2425:10.1002/j.1460-2075.1984.tb02106.x
14:
533:), and a C-terminal Ig-fold-like
2900:
1908:(Sixth ed.). New York, NY.
673:The experimental antitumor drug
290:
27:
853:(5326). New York, N.Y.: 690–3.
303:about newly-found IIB members .
1:
2286:10.1128/JVI.14.4.860-871.1974
1906:Molecular biology of the cell
1883:10.1016/s0959-440x(96)80099-6
433:a variable C-terminal domain.
217:. They use the hydrolysis of
2407:Cassuto E (September 1984).
2247:10.1016/0022-2836(76)90346-6
2235:Journal of Molecular Biology
2122:10.1016/0022-2836(79)90329-2
2110:Journal of Molecular Biology
1840:10.1016/0092-8674(94)90222-4
1038:Journal of Molecular Biology
859:10.1126/science.277.5326.690
2506:DNA+Topoisomerases,+Type+II
2143:Huang WM (September 1986).
467:accommodate the T-segment.
2939:
2376:10.1093/genetics/101.2.157
1970:10.1182/blood-2003-07-2527
1563:10.1038/s41467-019-12914-y
614:
2778:Michaelis–Menten kinetics
2336:10.1017/s0016672300031499
2184:Huang WM (October 1986).
1435:Nature Structural Biology
1050:10.1016/j.jmb.2005.06.029
953:10.3109/10409239109114072
821:10.3109/10409239109114072
151:
26:
2670:Diffusion-limited enzyme
2510:Medical Subject Headings
1904:Alberts B (2014-11-18).
705:during infection of the
2317:Hyman P (August 1993).
1631:10.1073/pnas.0401595101
1162:10.1073/pnas.1832879100
696:Bacteriophage T4 gyrase
617:Topoisomerase inhibitor
273:Topology simplification
2202:10.1093/nar/14.19.7751
2190:Nucleic Acids Research
2149:Nucleic Acids Research
2073:10.1073/pnas.76.8.3737
1264:10.1093/nar/26.18.4205
1252:Nucleic Acids Research
1216:10.1074/jbc.M506520200
993:10.1074/jbc.M101823200
907:10.1073/pnas.061029098
764:Nucleic Acids Research
522:
511:Structure of topo VI (
397:
379:
301:is missing information
203:Type II topoisomerases
2763:Eadie–Hofstee diagram
2696:Allosteric regulation
2577:Type II topoisomerase
1543:Nature Communications
722:genetic recombination
510:
385:
377:
2773:Lineweaver–Burk plot
2572:Type I topoisomerase
1691:10.1093/emboj/cdg008
688:(Serine79Alanine in
256:bacterial chromosome
223:Type I topoisomerase
2274:Journal of Virology
2064:1979PNAS...76.3737S
2009:1979Natur.281..456L
1736:1997Natur.386..414B
1622:2004PNAS..101.7293C
1555:2019NatCo..10.4935V
1508:10.1038/nature06396
1500:2007Natur.450.1201D
1384:1997Natur.388..903M
1319:1996Natur.379..225B
1153:2003PNAS..10010629C
1085:1991Natur.351..624W
898:2001PNAS...98.3045V
566:Mechanism of action
2732:Enzyme superfamily
2665:Enzyme promiscuity
2323:Genetical Research
776:10.1093/nar/gkn937
523:
406:GHKL ATPase domain
398:
380:
2888:
2887:
2597:
2596:
1915:978-0-8153-4432-2
324:
323:
200:
199:
196:
195:
115:metabolic pathway
2930:
2905:
2904:
2896:
2768:Hanes–Woolf plot
2711:Enzyme activator
2706:Enzyme inhibitor
2680:Enzyme catalysis
2624:
2617:
2610:
2601:
2587:topoisomerase IV
2540:
2533:
2526:
2517:
2494:
2447:
2446:
2436:
2413:The EMBO Journal
2404:
2398:
2397:
2387:
2355:
2349:
2348:
2338:
2314:
2308:
2307:
2297:
2265:
2259:
2258:
2230:
2224:
2223:
2213:
2181:
2175:
2174:
2164:
2140:
2134:
2133:
2105:
2096:
2095:
2085:
2075:
2043:
2037:
2036:
2017:10.1038/281456a0
2003:(5731): 456–61.
1989:
1983:
1982:
1972:
1948:
1942:
1941:
1935:
1927:
1901:
1895:
1894:
1866:
1860:
1859:
1823:
1817:
1816:
1797:10.1038/nsmb1264
1780:
1770:
1764:
1763:
1744:10.1038/386414a0
1719:
1713:
1712:
1702:
1679:The EMBO Journal
1670:
1660:
1654:
1653:
1643:
1633:
1601:
1591:
1585:
1584:
1574:
1534:
1528:
1527:
1494:(7173): 1201–5.
1483:
1473:
1467:
1466:
1430:
1420:
1414:
1413:
1395:
1363:
1353:
1347:
1346:
1327:10.1038/379225a0
1313:(6562): 225–32.
1302:
1292:
1286:
1285:
1275:
1243:
1237:
1236:
1218:
1200:
1191:
1185:
1184:
1174:
1164:
1147:(19): 10629–34.
1132:
1122:
1113:
1112:
1093:10.1038/351624a0
1068:
1062:
1061:
1033:
1023:
1014:
1013:
995:
986:(40): 37215–22.
971:
965:
964:
936:
930:
929:
919:
909:
877:
871:
870:
842:
833:
832:
815:(3–4): 335–375.
804:
798:
797:
787:
755:
520:
395:
336:topoisomerase IV
319:
316:
310:
294:
286:
153:
31:
19:
16:Class of enzymes
2938:
2937:
2933:
2932:
2931:
2929:
2928:
2927:
2913:
2912:
2911:
2899:
2891:
2889:
2884:
2796:Oxidoreductases
2782:
2758:Enzyme kinetics
2746:
2742:List of enzymes
2715:
2684:
2655:Catalytic triad
2633:
2628:
2598:
2593:
2558:
2544:
2502:
2497:
2460:
2456:
2454:Further reading
2451:
2450:
2406:
2405:
2401:
2357:
2356:
2352:
2316:
2315:
2311:
2267:
2266:
2262:
2232:
2231:
2227:
2196:(19): 7751–65.
2183:
2182:
2178:
2155:(18): 7379–90.
2142:
2141:
2137:
2107:
2106:
2099:
2045:
2044:
2040:
1991:
1990:
1986:
1963:(12): 4659–65.
1950:
1949:
1945:
1928:
1916:
1903:
1902:
1898:
1868:
1867:
1863:
1825:
1824:
1820:
1782:
1772:
1771:
1767:
1730:(6623): 414–7.
1721:
1720:
1716:
1672:
1662:
1661:
1657:
1603:
1593:
1592:
1588:
1536:
1535:
1531:
1485:
1475:
1474:
1470:
1432:
1422:
1421:
1417:
1378:(6645): 903–6.
1365:
1355:
1354:
1350:
1304:
1294:
1293:
1289:
1258:(18): 4205–13.
1245:
1244:
1240:
1209:(44): 37041–7.
1198:
1193:
1192:
1188:
1134:
1124:
1123:
1116:
1079:(6328): 624–9.
1070:
1069:
1065:
1035:
1025:
1024:
1017:
973:
972:
968:
947:(3–4): 335–75.
938:
937:
933:
879:
878:
874:
844:
843:
836:
806:
805:
801:
757:
756:
752:
747:
703:DNA replication
698:
619:
613:
597:
588:
573:
568:
512:
505:
448:
444:
440:
387:
372:
367:
320:
314:
311:
304:
295:
284:
275:
250:and most other
238:
34:
17:
12:
11:
5:
2936:
2934:
2926:
2925:
2915:
2914:
2910:
2909:
2886:
2885:
2883:
2882:
2869:
2856:
2843:
2830:
2817:
2804:
2790:
2788:
2784:
2783:
2781:
2780:
2775:
2770:
2765:
2760:
2754:
2752:
2748:
2747:
2745:
2744:
2739:
2734:
2729:
2723:
2721:
2720:Classification
2717:
2716:
2714:
2713:
2708:
2703:
2698:
2692:
2690:
2686:
2685:
2683:
2682:
2677:
2672:
2667:
2662:
2657:
2652:
2647:
2641:
2639:
2635:
2634:
2629:
2627:
2626:
2619:
2612:
2604:
2595:
2594:
2592:
2591:
2590:
2589:
2584:
2574:
2568:
2566:
2560:
2559:
2551:topoisomerases
2545:
2543:
2542:
2535:
2528:
2520:
2514:
2513:
2501:
2500:External links
2498:
2496:
2495:
2475:10.1038/nrm831
2457:
2455:
2452:
2449:
2448:
2419:(9): 2159–64.
2399:
2350:
2309:
2260:
2225:
2176:
2135:
2097:
2058:(8): 3737–41.
2038:
1984:
1943:
1914:
1896:
1861:
1818:
1765:
1714:
1655:
1616:(19): 7293–8.
1586:
1529:
1468:
1415:
1348:
1287:
1238:
1186:
1114:
1063:
1015:
966:
931:
872:
834:
799:
770:(3): 738–748.
749:
748:
746:
743:
697:
694:
671:
670:
643:
615:Main article:
612:
609:
596:
593:
587:
584:
572:
571:Strand passage
569:
567:
564:
504:
501:
446:
442:
438:
435:
434:
431:
428:
409:
404:an N-terminal
371:
368:
366:
363:
343:
342:
339:
322:
321:
298:
296:
289:
283:
282:Classification
280:
274:
271:
237:
234:
227:linking number
207:topoisomerases
198:
197:
194:
193:
188:
182:
181:
176:
170:
169:
164:
158:
157:
149:
148:
137:
130:
129:
124:
118:
117:
112:
106:
105:
100:
94:
93:
88:
82:
81:
76:
70:
69:
64:
58:
57:
53:
52:
47:
41:
40:
36:
35:
32:
24:
23:
15:
13:
10:
9:
6:
4:
3:
2:
2935:
2924:
2921:
2920:
2918:
2908:
2903:
2898:
2894:
2880:
2876:
2875:
2870:
2867:
2863:
2862:
2857:
2854:
2850:
2849:
2844:
2841:
2837:
2836:
2831:
2828:
2824:
2823:
2818:
2815:
2811:
2810:
2805:
2802:
2798:
2797:
2792:
2791:
2789:
2785:
2779:
2776:
2774:
2771:
2769:
2766:
2764:
2761:
2759:
2756:
2755:
2753:
2749:
2743:
2740:
2738:
2737:Enzyme family
2735:
2733:
2730:
2728:
2725:
2724:
2722:
2718:
2712:
2709:
2707:
2704:
2702:
2701:Cooperativity
2699:
2697:
2694:
2693:
2691:
2687:
2681:
2678:
2676:
2673:
2671:
2668:
2666:
2663:
2661:
2660:Oxyanion hole
2658:
2656:
2653:
2651:
2648:
2646:
2643:
2642:
2640:
2636:
2632:
2625:
2620:
2618:
2613:
2611:
2606:
2605:
2602:
2588:
2585:
2583:
2580:
2579:
2578:
2575:
2573:
2570:
2569:
2567:
2565:
2561:
2556:
2552:
2548:
2541:
2536:
2534:
2529:
2527:
2522:
2521:
2518:
2511:
2507:
2504:
2503:
2499:
2492:
2488:
2484:
2480:
2476:
2472:
2469:(6): 430–40.
2468:
2464:
2459:
2458:
2453:
2444:
2440:
2435:
2430:
2426:
2422:
2418:
2414:
2410:
2403:
2400:
2395:
2391:
2386:
2381:
2377:
2373:
2370:(2): 157–77.
2369:
2365:
2361:
2354:
2351:
2346:
2342:
2337:
2332:
2328:
2324:
2320:
2313:
2310:
2305:
2301:
2296:
2291:
2287:
2283:
2280:(4): 860–71.
2279:
2275:
2271:
2264:
2261:
2256:
2252:
2248:
2244:
2241:(4): 963–81.
2240:
2236:
2229:
2226:
2221:
2217:
2212:
2207:
2203:
2199:
2195:
2191:
2187:
2180:
2177:
2172:
2168:
2163:
2158:
2154:
2150:
2146:
2139:
2136:
2131:
2127:
2123:
2119:
2116:(3): 265–83.
2115:
2111:
2104:
2102:
2098:
2093:
2089:
2084:
2079:
2074:
2069:
2065:
2061:
2057:
2053:
2049:
2042:
2039:
2034:
2030:
2026:
2022:
2018:
2014:
2010:
2006:
2002:
1998:
1994:
1988:
1985:
1980:
1976:
1971:
1966:
1962:
1958:
1954:
1947:
1944:
1939:
1933:
1925:
1921:
1917:
1911:
1907:
1900:
1897:
1892:
1888:
1884:
1880:
1876:
1872:
1865:
1862:
1857:
1853:
1849:
1845:
1841:
1837:
1834:(4): 609–16.
1833:
1829:
1822:
1819:
1814:
1810:
1806:
1802:
1798:
1794:
1790:
1786:
1779:
1775:
1769:
1766:
1761:
1757:
1753:
1749:
1745:
1741:
1737:
1733:
1729:
1725:
1718:
1715:
1710:
1706:
1701:
1696:
1692:
1688:
1685:(1): 151–63.
1684:
1680:
1676:
1669:
1665:
1659:
1656:
1651:
1647:
1642:
1637:
1632:
1627:
1623:
1619:
1615:
1611:
1607:
1600:
1596:
1590:
1587:
1582:
1578:
1573:
1568:
1564:
1560:
1556:
1552:
1548:
1544:
1540:
1533:
1530:
1525:
1521:
1517:
1513:
1509:
1505:
1501:
1497:
1493:
1489:
1482:
1478:
1472:
1469:
1464:
1460:
1456:
1452:
1448:
1444:
1440:
1436:
1429:
1425:
1419:
1416:
1411:
1407:
1403:
1399:
1394:
1393:10.1038/42294
1389:
1385:
1381:
1377:
1373:
1369:
1362:
1358:
1352:
1349:
1344:
1340:
1336:
1332:
1328:
1324:
1320:
1316:
1312:
1308:
1301:
1297:
1291:
1288:
1283:
1279:
1274:
1269:
1265:
1261:
1257:
1253:
1249:
1242:
1239:
1234:
1230:
1226:
1222:
1217:
1212:
1208:
1204:
1197:
1190:
1187:
1182:
1178:
1173:
1168:
1163:
1158:
1154:
1150:
1146:
1142:
1138:
1131:
1127:
1121:
1119:
1115:
1110:
1106:
1102:
1098:
1094:
1090:
1086:
1082:
1078:
1074:
1067:
1064:
1059:
1055:
1051:
1047:
1044:(3): 545–61.
1043:
1039:
1032:
1028:
1022:
1020:
1016:
1011:
1007:
1003:
999:
994:
989:
985:
981:
977:
970:
967:
962:
958:
954:
950:
946:
942:
935:
932:
927:
923:
918:
913:
908:
903:
899:
895:
892:(6): 3045–9.
891:
887:
883:
876:
873:
868:
864:
860:
856:
852:
848:
841:
839:
835:
830:
826:
822:
818:
814:
810:
803:
800:
795:
791:
786:
781:
777:
773:
769:
765:
761:
754:
751:
744:
742:
740:
735:
731:
727:
723:
718:
714:
710:
709:
704:
695:
693:
691:
687:
683:
678:
676:
668:
664:
663:ciprofloxacin
660:
656:
652:
648:
644:
641:
637:
633:
629:
625:
624:
623:
618:
610:
608:
606:
601:
594:
592:
585:
583:
580:
576:
570:
565:
563:
559:
556:
552:
550:
547:
543:
540:
536:
532:
529:
519:
515:
509:
502:
500:
496:
492:
490:
486:
480:
476:
472:
468:
464:
462:
459:
455:
452:
432:
429:
426:
422:
418:
417:Rossmann fold
414:
413:Toprim domain
410:
407:
403:
402:
401:
394:
390:
384:
376:
369:
364:
362:
358:
356:
352:
348:
340:
337:
333:
329:
328:
327:
318:
308:
302:
299:This section
297:
293:
288:
287:
281:
279:
272:
270:
266:
263:
261:
257:
253:
249:
248:
243:
235:
233:
230:
228:
224:
220:
216:
212:
208:
204:
192:
189:
187:
183:
180:
177:
175:
171:
168:
165:
163:
159:
154:
150:
147:
144:
141:
138:
135:
131:
128:
125:
123:
119:
116:
113:
111:
107:
104:
101:
99:
95:
92:
91:NiceZyme view
89:
87:
83:
80:
77:
75:
71:
68:
65:
63:
59:
54:
51:
48:
46:
42:
37:
30:
25:
20:
2874:Translocases
2871:
2858:
2845:
2832:
2819:
2809:Transferases
2806:
2793:
2650:Binding site
2576:
2466:
2462:
2416:
2412:
2402:
2367:
2363:
2353:
2326:
2322:
2312:
2277:
2273:
2263:
2238:
2234:
2228:
2193:
2189:
2179:
2152:
2148:
2138:
2113:
2109:
2055:
2051:
2041:
2000:
1996:
1987:
1960:
1956:
1946:
1905:
1899:
1877:(1): 84–90.
1874:
1870:
1864:
1831:
1827:
1821:
1791:(7): 611–9.
1788:
1784:
1768:
1727:
1723:
1717:
1682:
1678:
1658:
1613:
1609:
1589:
1546:
1542:
1532:
1491:
1487:
1471:
1447:10.1038/7556
1441:(4): 322–6.
1438:
1434:
1418:
1375:
1371:
1351:
1310:
1306:
1290:
1255:
1251:
1241:
1206:
1202:
1189:
1144:
1140:
1076:
1072:
1066:
1041:
1037:
983:
979:
969:
944:
940:
934:
889:
885:
875:
850:
846:
812:
808:
802:
767:
763:
753:
738:
716:
712:
706:
699:
689:
679:
672:
620:
598:
589:
586:DNA cleavage
581:
577:
574:
560:
557:
553:
524:
497:
493:
484:
481:
477:
473:
469:
465:
436:
399:
359:
344:
325:
315:October 2021
312:
300:
276:
267:
264:
245:
239:
231:
213:tangles and
202:
201:
79:BRENDA entry
2645:Active site
1549:(1): 4935.
730:ultraviolet
661:(including
647:doxorubicin
640:mitindomide
535:H2TH domain
489:gepotidacin
252:prokaryotes
67:IntEnz view
39:Identifiers
2848:Isomerases
2822:Hydrolases
2689:Regulation
2329:(1): 1–9.
745:References
734:chromosome
682:eukaryotic
667:teniposide
659:quinolones
655:novobiocin
611:Inhibition
605:eukaryotes
600:Catenation
595:Catenation
332:DNA gyrase
260:supercoils
242:DNA gyrase
215:supercoils
136:structures
103:KEGG entry
2923:EC 5.99.1
2727:EC number
2547:Isomerase
2491:205496065
1932:cite book
1924:887605755
1781:;
1671:;
1602:;
1484:;
1431:;
1364:;
1303:;
1133:;
1034:;
651:etoposide
365:Structure
307:talk page
221:, unlike
56:Databases
2917:Category
2751:Kinetics
2675:Cofactor
2638:Activity
2483:12042765
2364:Genetics
1979:15010369
1856:19776252
1805:17603498
1709:12505993
1650:15123801
1581:31666516
1516:18097402
1455:10201398
1233:35186716
1225:16100112
1181:12963818
1058:16023670
1010:24354635
1002:11485995
926:11248029
794:19042970
726:mutation
636:ICRF-193
632:ICRF-187
503:Type IIB
370:Type IIA
236:Function
191:proteins
179:articles
167:articles
140:RCSB PDB
2907:Biology
2861:Ligases
2631:Enzymes
2443:6092061
2394:6293912
2385:1201854
2345:8405988
2304:4609406
2220:3022233
2171:3020513
2060:Bibcode
2033:4343962
2005:Bibcode
1891:8696977
1848:8187179
1813:2159631
1760:4327493
1752:9121560
1732:Bibcode
1618:Bibcode
1572:6821735
1551:Bibcode
1524:1756317
1496:Bibcode
1410:4320715
1402:9278055
1380:Bibcode
1343:4360011
1335:8538787
1315:Bibcode
1282:9722641
1149:Bibcode
1109:4373125
1101:1646964
1081:Bibcode
961:1657531
894:Bibcode
867:9235892
847:Science
829:1657531
785:2647315
739:E. coli
717:E. coli
713:E. coli
708:E. coli
690:E. coli
665:), and
549:PF04406
542:PF18000
531:PF09239
485:E. coli
461:PF00521
454:PF00204
421:primase
355:cancers
247:E. coli
127:profile
110:MetaCyc
50:5.6.2.2
2893:Portal
2835:Lyases
2582:gyrase
2512:(MeSH)
2489:
2481:
2441:
2434:557658
2431:
2392:
2382:
2343:
2302:
2295:355592
2292:
2255:789903
2253:
2218:
2211:311794
2208:
2169:
2162:311757
2159:
2130:372540
2128:
2092:226976
2090:
2083:383908
2080:
2031:
2025:226889
2023:
1997:Nature
1993:Liu LF
1977:
1922:
1912:
1889:
1854:
1846:
1811:
1803:
1758:
1750:
1724:Nature
1707:
1700:140052
1697:
1648:
1641:409912
1638:
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1569:
1522:
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1488:Nature
1463:947461
1461:
1453:
1408:
1400:
1372:Nature
1341:
1333:
1307:Nature
1280:
1273:147817
1270:
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1179:
1172:196855
1169:
1107:
1099:
1073:Nature
1056:
1008:
1000:
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924:
914:
865:
827:
792:
782:
686:gyrase
675:m-AMSA
638:, and
628:HU-331
174:PubMed
156:Search
146:PDBsum
86:ExPASy
74:BRENDA
62:IntEnz
45:EC no.
2787:Types
2564:5.6.2
2487:S2CID
2029:S2CID
1957:Blood
1852:S2CID
1809:S2CID
1756:S2CID
1520:S2CID
1459:S2CID
1406:S2CID
1339:S2CID
1229:S2CID
1199:(PDF)
1105:S2CID
1006:S2CID
917:30604
353:. In
347:alpha
122:PRIAM
2879:list
2872:EC7
2866:list
2859:EC6
2853:list
2846:EC5
2840:list
2833:EC4
2827:list
2820:EC3
2814:list
2807:EC2
2801:list
2794:EC1
2557:5.6)
2479:PMID
2439:PMID
2390:PMID
2341:PMID
2300:PMID
2251:PMID
2216:PMID
2167:PMID
2126:PMID
2088:PMID
2021:PMID
1975:PMID
1938:link
1920:OCLC
1910:ISBN
1887:PMID
1844:PMID
1828:Cell
1801:PMID
1778:2Q2E
1748:PMID
1705:PMID
1668:1MU5
1646:PMID
1599:1SUU
1577:PMID
1512:PMID
1481:2RGR
1451:PMID
1428:1BJT
1398:PMID
1361:1AB4
1331:PMID
1300:1BGW
1278:PMID
1221:PMID
1177:PMID
1130:1PVG
1097:PMID
1054:PMID
1031:1zvt
998:PMID
957:PMID
922:PMID
863:PMID
825:PMID
790:PMID
546:Pfam
539:Pfam
528:Pfam
518:2Q2E
458:Pfam
451:Pfam
425:DnaG
393:2RGR
351:beta
349:and
205:are
186:NCBI
143:PDBe
98:KEGG
2471:doi
2429:PMC
2421:doi
2380:PMC
2372:doi
2368:101
2331:doi
2290:PMC
2282:doi
2243:doi
2239:106
2206:PMC
2198:doi
2157:PMC
2118:doi
2114:127
2078:PMC
2068:doi
2013:doi
2001:281
1965:doi
1961:103
1879:doi
1836:doi
1793:doi
1774:PDB
1740:doi
1728:386
1695:PMC
1687:doi
1664:PDB
1636:PMC
1626:doi
1614:101
1595:PDB
1567:PMC
1559:doi
1504:doi
1492:450
1477:PDB
1443:doi
1424:PDB
1388:doi
1376:388
1357:PDB
1323:doi
1311:379
1296:PDB
1268:PMC
1260:doi
1211:doi
1207:280
1167:PMC
1157:doi
1145:100
1126:PDB
1089:doi
1077:351
1046:doi
1042:351
1027:PDB
988:doi
984:276
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817:doi
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