Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTNJKC3)

DTT Name	Leishmania DNA topoisomerase I (Leishm TOP1)
Synonyms	Leishm DNA topoisomerase I; DNA topoisomerase 1
Gene Name	Leishm TOP1
DTT Type	Clinical trial target	[1]
UniProt ID	Q9NJG8_LEIDO
TTD ID	T31329
EC Number	EC 5.6.2.2
Sequence	MPLPGGGTEVLKGITLLTQHHGLKPVQPMSFCYLSFLNRHTHEHHLRLHCCRPHAYARAH PCTCLIDFPLTSYPISQQCAPRLLPLPRQPPLSSQPAEAPSQIGTKDGLLLFRVSNRPQW VFCVCVCVRACPSFPLPRSCDFNRRGAVSPLSSPPRRAPVCCWRFFFHSCSFFFLVLYLL SAPYFCSLWARCANEEDKQNKLRIKQHETKKETPFRVCGGDCPSCCVGLSSHLFFPRWRL LVPPLPYTLDSNNSIFCVFHLFIYFLVCLFVSLAPSTYPFVPLCQLRTLHLYEPRPHIGT PLRCFCCHRDSIRRIMKVENSKMGVKREQSHSNEDEEINEEDLNWWEQENLRIAMKGERR WETLAHNGVLFPPEYEPHGIPIFYDGREFKMTPEEEEVATMFAVMKEHDYYRMEVFRRNF FESWREILDKRQHPIRRLELCDFEPIYQWHLVQREKKLSRTKEEKKAIKEKQDAEAEPYR YCVWDGRREQVANFRVEPPGLFRGRGKHPLMGKLKVRVQPEDITINIGETAEVPVPPAGH KWAAVQHDHTVTWLAMWRDSVAGNMKYVMLAPSSSVKGQSDMVKFEKARKLKDKVDDIRA SYMEDFKSNDLHVAQRAVAMYIDRLALRVGNEKGEDEADTVGCCSLRVEHIQLMPDNIVR FDFLGKDSIRYQNDVAVLPEVYALLQRFTRRKSPGMDIFDQLNPTQLNDHLKSFMDGLSA KVFRTYNASITLDRWFKEKPVDPKWSTADKLAYFNKANTEVAILCNHQKSVSKNFKLQMM QLTTKSEYTRKTIELLEKAEVTAKKKSVEEAAKEFLEEQDRMQREWLESYGTEEQKKEFE EIVAKRAAPRVRSEKKKSTSGAKKAESASGKKRAAKKKKSAKKGGKMLSKKAASKSSKKA PKKLKEEDEDDVPLVSVAAKTKKTAGVKRQRANKVVSDDDDVPLAALRV
Function	Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at the specific target site 5'-[CT]CCTTp site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone.

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sodium stibogluconate	DMH5MVE	Advanced cancer	2A00-2F9Z	Phase 2	[1]
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References

1	Inhibition of Leishmania donovani promastigote DNA topoisomerase I and human monocyte DNA topoisomerases I and II by antimonial drugs and classical antitopoisomerase agents. J Parasitol. 2004 Oct;90(5):1155-62.