TARGETID

T31329

FORMERID

TTDI01928

UNIPROID

Q9NJG8_LEIDO

TARGNAME

Leishmania DNA topoisomerase I (Leishm TOP1)

GENENAME

Leishm TOP1

TARGTYPE

Clinical trial target

SYNONYMS

Leishm DNA topoisomerase I; DNA topoisomerase 1

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.

ECNUMBER

EC 5.6.2.2

SEQUENCE

MPLPGGGTEVLKGITLLTQHHGLKPVQPMSFCYLSFLNRHTHEHHLRLHCCRPHAYARAHPCTCLIDFPLTSYPISQQCAPRLLPLPRQPPLSSQPAEAPSQIGTKDGLLLFRVSNRPQWVFCVCVCVRACPSFPLPRSCDFNRRGAVSPLSSPPRRAPVCCWRFFFHSCSFFFLVLYLLSAPYFCSLWARCANEEDKQNKLRIKQHETKKETPFRVCGGDCPSCCVGLSSHLFFPRWRLLVPPLPYTLDSNNSIFCVFHLFIYFLVCLFVSLAPSTYPFVPLCQLRTLHLYEPRPHIGTPLRCFCCHRDSIRRIMKVENSKMGVKREQSHSNEDEEINEEDLNWWEQENLRIAMKGERRWETLAHNGVLFPPEYEPHGIPIFYDGREFKMTPEEEEVATMFAVMKEHDYYRMEVFRRNFFESWREILDKRQHPIRRLELCDFEPIYQWHLVQREKKLSRTKEEKKAIKEKQDAEAEPYRYCVWDGRREQVANFRVEPPGLFRGRGKHPLMGKLKVRVQPEDITINIGETAEVPVPPAGHKWAAVQHDHTVTWLAMWRDSVAGNMKYVMLAPSSSVKGQSDMVKFEKARKLKDKVDDIRASYMEDFKSNDLHVAQRAVAMYIDRLALRVGNEKGEDEADTVGCCSLRVEHIQLMPDNIVRFDFLGKDSIRYQNDVAVLPEVYALLQRFTRRKSPGMDIFDQLNPTQLNDHLKSFMDGLSAKVFRTYNASITLDRWFKEKPVDPKWSTADKLAYFNKANTEVAILCNHQKSVSKNFKLQMMQLTTKSEYTRKTIELLEKAEVTAKKKSVEEAAKEFLEEQDRMQREWLESYGTEEQKKEFEEIVAKRAAPRVRSEKKKSTSGAKKAESASGKKRAAKKKKSAKKGGKMLSKKAASKSSKKAPKKLKEEDEDDVPLVSVAAKTKKTAGVKRQRANKVVSDDDDVPLAALRV

DRUGINFO

Sodium stibogluconate