Topoisomerase

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Topoisomerase I complex with DNA and phosphotyrosine (PDB entry 2h7f)

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Function

Topoisomerase or DNA topoisomerase (TOP) winds and unwinds DNA double helix in order to enable DNA replication. The reaction catalyzed by topoisomerases leads to the conversion of one topological isomer of DNA to another^[1].

TOPI cuts one strand of the double helix. It has 3 subclasses: TOPIA which shares its mechanism with TOPII and TOPIB which uses rotary mechanism and includes topo I and topo III. TOPIC called TOPV shares its mechanism with TOPIB but is structurally unique. See also

Variola Topoisomerase 1B
Smallpox (Variola Virus) - Topoisomerase 1B.

TOPII or DNA gyrase cuts both strands of the double helix. Its subclasses are TOPIIA including topo II and TOPIIB which includes topo VI.
TOPIII is a potent decatenase.
TOPIV is a type of TOPII, contains an ATP-binding domain ParE (subunit B) and a catalytic domain ParC (subunit A).
TOPV is a type of TOPI from hyperthermophilic prokaryotes.
^[2]

Relevance

TOP!V inhibitors Ciprofloxacin and Avelox (moxifloxacin) are used as antibacterial antibiotics. See Avelox (moxifloxacin).

Disease

TOPIIA is highly expressed in colorectal cancer^[3]. TOP inhibitors are explored as potential therapeutic agents for treatment of infectious diseases^[4].

3D Structures of Topoisomerase

Topoisomerase 3D structures

↑ Champoux JJ. DNA topoisomerases: structure, function, and mechanism. Annu Rev Biochem. 2001;70:369-413. PMID:11395412 doi:https://dx.doi.org/10.1146/annurev.biochem.70.1.369
↑ Slesarev AI, Stetter KO, Lake JA, Gellert M, Krah R, Kozyavkin SA. DNA topoisomerase V is a relative of eukaryotic topoisomerase I from a hyperthermophilic prokaryote. Nature. 1993 Aug 19;364(6439):735-7. PMID:8395022 doi:https://dx.doi.org/10.1038/364735a0
↑ Coss A, Tosetto M, Fox EJ, Sapetto-Rebow B, Gorman S, Kennedy BN, Lloyd AT, Hyland JM, O'Donoghue DP, Sheahan K, Leahy DT, Mulcahy HE, O'Sullivan JN. Increased topoisomerase IIalpha expression in colorectal cancer is associated with advanced disease and chemotherapeutic resistance via inhibition of apoptosis. Cancer Lett. 2009 Apr 18;276(2):228-38. doi: 10.1016/j.canlet.2008.11.018. Epub, 2008 Dec 25. PMID:19111388 doi:https://dx.doi.org/10.1016/j.canlet.2008.11.018
↑ Tse-Dinh YC. Exploring DNA topoisomerases as targets of novel therapeutic agents in the treatment of infectious diseases. Infect Disord Drug Targets. 2007 Mar;7(1):3-9. PMID:17346206

GO Annotations

Database	ID	Symbol	GO Identifier	GO Term Name	Aspect	Evidence	Reference	With	Taxon	Date	Assigned by
UniProtKB	P14294	topB	GO:0006259	DNA metabolic process	P	IEA	InterPro2GO	InterPro:IPR006154	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0006265	DNA topological change	P	IEA	InterPro2GO	InterPro:IPR000380	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0006265	DNA topological change	P	IEA	InterPro2GO	InterPro:IPR003601	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0006265	DNA topological change	P	IEA	InterPro2GO	InterPro:IPR003602	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0006265	DNA topological change	P	IEA	InterPro2GO	InterPro:IPR005738	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0006265	DNA topological change	P	IEA	InterPro2GO	InterPro:IPR013497	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0006265	DNA topological change	P	IEA	InterPro2GO	InterPro:IPR013824	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0006265	DNA topological change	P	IEA	InterPro2GO	InterPro:IPR013825	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0006268	DNA unwinding involved in replication	P	IEA	InterPro2GO	InterPro:IPR013824	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0006268	DNA unwinding involved in replication	P	IEA	InterPro2GO	InterPro:IPR013825	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0000166	nucleotide binding	F	IEA	Swiss-Prot Keywords2GO	SP_KW:KW-0547	83333	20101127	UniProtKB
UniProtKB	P14294	topB	GO:0003676	nucleic acid binding	F	IEA	InterPro2GO	InterPro:IPR006154	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0003677	DNA binding	F	IEA	InterPro2GO	InterPro:IPR000380	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0003677	DNA binding	F	IEA	InterPro2GO	InterPro:IPR003601	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0003677	DNA binding	F	IEA	InterPro2GO	InterPro:IPR003602	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0003677	DNA binding	F	IEA	InterPro2GO	InterPro:IPR005738	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0003677	DNA binding	F	IEA	InterPro2GO	InterPro:IPR013497	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0003677	DNA binding	F	IEA	InterPro2GO	InterPro:IPR013824	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0003677	DNA binding	F	IEA	InterPro2GO	InterPro:IPR013825	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0003677	DNA binding	F	IEA	Swiss-Prot Keywords2GO	SP_KW:KW-0238	83333	20101127	UniProtKB
UniProtKB	P14294	topB	GO:0003916	DNA topoisomerase activity	F	IEA	InterPro2GO	InterPro:IPR003601	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0003916	DNA topoisomerase activity	F	IEA	InterPro2GO	InterPro:IPR003602	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0003916	DNA topoisomerase activity	F	IEA	InterPro2GO	InterPro:IPR005738	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0003916	DNA topoisomerase activity	F	IEA	InterPro2GO	InterPro:IPR013497	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0003916	DNA topoisomerase activity	F	IEA	InterPro2GO	InterPro:IPR013824	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0003916	DNA topoisomerase activity	F	IEA	InterPro2GO	InterPro:IPR013825	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0003916	DNA topoisomerase activity	F	IEA	Swiss-Prot Keywords2GO	SP_KW:KW-0799	83333	20101127	UniProtKB
UniProtKB	P14294	topB	GO:0003917	DNA topoisomerase type I activity	F	IDA	PMID:6326814		83333	20100621	EcoliWiki
UniProtKB	P14294	topB	GO:0003917	DNA topoisomerase type I activity	F	IEA	InterPro2GO	InterPro:IPR000380	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0003917	DNA topoisomerase type I activity	F	IEA	EC2GO	EC:5.99.1.2	83333	20100703	UniProtKB
UniProtKB	P14294	topB	GO:0005515	protein binding	F	IPI	PMID:15690043	frlR (FRLR_ECOLI)	83333	20101127	IntAct
UniProtKB	P14294	topB	GO:0005524	ATP binding	F	IEA	Swiss-Prot Keywords2GO	SP_KW:KW-0067	83333	20101127	UniProtKB
UniProtKB	P14294	topB	GO:0016853	isomerase activity	F	IEA	Swiss-Prot Keywords2GO	SP_KW:KW-0413	83333	20101127	UniProtKB
UniProtKB	P14294	topB	GO:0005694	chromosome	C	IEA	InterPro2GO	InterPro:IPR000380	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0005694	chromosome	C	IEA	InterPro2GO	InterPro:IPR003601	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0005694	chromosome	C	IEA	InterPro2GO	InterPro:IPR003602	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0005694	chromosome	C	IEA	InterPro2GO	InterPro:IPR005738	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0005694	chromosome	C	IEA	InterPro2GO	InterPro:IPR013497	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0005694	chromosome	C	IEA	InterPro2GO	InterPro:IPR013824	83333	20101127	InterPro
UniProtKB	P14294	topB	GO:0005694	chromosome	C	IEA	InterPro2GO	InterPro:IPR013825	83333	20101127	InterPro

Copied from [1] Last updated Dec 2 2010

References

Created with the participation of Sonny Zhao.

Proteopedia Page Contributors and Editors (what is this?)

Alexander Berchansky, Joel L. Sussman, Jaime Prilusky, Michal Harel

[1] Champoux JJ. DNA topoisomerases: structure, function, and mechanism. Annu Rev Biochem. 2001;70:369-413. PMID:11395412 doi:https://dx.doi.org/10.1146/annurev.biochem.70.1.369

[2] Slesarev AI, Stetter KO, Lake JA, Gellert M, Krah R, Kozyavkin SA. DNA topoisomerase V is a relative of eukaryotic topoisomerase I from a hyperthermophilic prokaryote. Nature. 1993 Aug 19;364(6439):735-7. PMID:8395022 doi:https://dx.doi.org/10.1038/364735a0

[3] Coss A, Tosetto M, Fox EJ, Sapetto-Rebow B, Gorman S, Kennedy BN, Lloyd AT, Hyland JM, O'Donoghue DP, Sheahan K, Leahy DT, Mulcahy HE, O'Sullivan JN. Increased topoisomerase IIalpha expression in colorectal cancer is associated with advanced disease and chemotherapeutic resistance via inhibition of apoptosis. Cancer Lett. 2009 Apr 18;276(2):228-38. doi: 10.1016/j.canlet.2008.11.018. Epub, 2008 Dec 25. PMID:19111388 doi:https://dx.doi.org/10.1016/j.canlet.2008.11.018

[4] Tse-Dinh YC. Exploring DNA topoisomerases as targets of novel therapeutic agents in the treatment of infectious diseases. Infect Disord Drug Targets. 2007 Mar;7(1):3-9. PMID:17346206

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Topoisomerase

Contents

Function

Relevance

Disease

3D Structures of Topoisomerase

GO Annotations

References

Proteopedia Page Contributors and Editors (what is this?)

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