Target Information
| Target General Information | Top | |||||
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| Target ID |
T31329
(Former ID: TTDI01928)
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| Target Name |
Leishmania DNA topoisomerase I (Leishm TOP1)
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| Synonyms |
Leishm DNA topoisomerase I; DNA topoisomerase 1
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| Gene Name |
Leishm TOP1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| 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.
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| UniProt ID | ||||||
| EC Number |
EC 5.6.2.2
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| Sequence |
MPLPGGGTEVLKGITLLTQHHGLKPVQPMSFCYLSFLNRHTHEHHLRLHCCRPHAYARAH
PCTCLIDFPLTSYPISQQCAPRLLPLPRQPPLSSQPAEAPSQIGTKDGLLLFRVSNRPQW VFCVCVCVRACPSFPLPRSCDFNRRGAVSPLSSPPRRAPVCCWRFFFHSCSFFFLVLYLL SAPYFCSLWARCANEEDKQNKLRIKQHETKKETPFRVCGGDCPSCCVGLSSHLFFPRWRL LVPPLPYTLDSNNSIFCVFHLFIYFLVCLFVSLAPSTYPFVPLCQLRTLHLYEPRPHIGT PLRCFCCHRDSIRRIMKVENSKMGVKREQSHSNEDEEINEEDLNWWEQENLRIAMKGERR WETLAHNGVLFPPEYEPHGIPIFYDGREFKMTPEEEEVATMFAVMKEHDYYRMEVFRRNF FESWREILDKRQHPIRRLELCDFEPIYQWHLVQREKKLSRTKEEKKAIKEKQDAEAEPYR YCVWDGRREQVANFRVEPPGLFRGRGKHPLMGKLKVRVQPEDITINIGETAEVPVPPAGH KWAAVQHDHTVTWLAMWRDSVAGNMKYVMLAPSSSVKGQSDMVKFEKARKLKDKVDDIRA SYMEDFKSNDLHVAQRAVAMYIDRLALRVGNEKGEDEADTVGCCSLRVEHIQLMPDNIVR FDFLGKDSIRYQNDVAVLPEVYALLQRFTRRKSPGMDIFDQLNPTQLNDHLKSFMDGLSA KVFRTYNASITLDRWFKEKPVDPKWSTADKLAYFNKANTEVAILCNHQKSVSKNFKLQMM QLTTKSEYTRKTIELLEKAEVTAKKKSVEEAAKEFLEEQDRMQREWLESYGTEEQKKEFE EIVAKRAAPRVRSEKKKSTSGAKKAESASGKKRAAKKKKSAKKGGKMLSKKAASKSSKKA PKKLKEEDEDDVPLVSVAAKTKKTAGVKRQRANKVVSDDDDVPLAALRV Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | Sodium stibogluconate | Drug Info | Phase 2 | Solid tumour/cancer | [1], [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | Sodium stibogluconate | Drug Info | [1], [2] | |||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
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There is no similarity protein (E value < 0.005) for this target
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| Target Regulators | Top | |||||
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| Target-regulating Transcription Factors | ||||||
| References | Top | |||||
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| REF 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. | |||||
| REF 2 | Mode of action of pentavalent antimonials: specific inhibition of type I DNA topoisomerase of Leishmania donovani. Biochem Biophys Res Commun. 1988 Apr 29;152(2):605-11. | |||||
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