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Literature summary for 5.6.2.1 extracted from

  • Diaz Gonzalez, R.; Perez Pertejo, Y.; Redondo, C.M.; Pommier, Y.; Balana-Fouce, R.; Reguera, R.M.
    Structural insights on the small subunit of DNA topoisomerase I from the unicellular parasite Leishmania donovani (2007), Biochimie, 89, 1517-1527.
    View publication on PubMed

Application

Application Comment Organism
drug development DNA topoisomerase I is an important cellular target in drug discovery Leishmania donovani

Cloned(Commentary)

Cloned (Comment) Organism
Heterologous co-expression of LdTop1L and LdTop1S in a topoisomerase I deficient Saccharomyces cerevisiae strain (EKY3, MBY3), reconstitutes a fully functional enzyme which can be used for structural studies. Purified fragments of N-terminal truncation are used to transform XL-1Blue Escherichia coli Leishmania donovani

Protein Variants

Protein Variants Comment Organism
delta 175-262 N-terminal truncation performed on LdTop1S subunits Leishmania donovani
delta 180-262 N-terminal truncation performed on LdTop1S subunits Leishmania donovani
delta 182-262 N-terminal truncation performed on LdTop1S subunits Leishmania donovani
delta 200-262 N-terminal truncation performed on LdTop1S subunits Leishmania donovani
delta 210-262 N-terminal truncation performed on LdTop1S subunits Leishmania donovani

Inhibitors

Inhibitors Comment Organism Structure
camptothecin Wild type and mutant sensitivity to camptothecin is determined in DNA cleavage assays. In vivo sensitivity to camptothecin also measured Leishmania donovani
additional information trapping of the covalent complex between LdTop1 and DNA by camptothecin resides in a pentapeptide placed upwards Arg-180, increases the sensitivity to the poison Leishmania donovani

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
28000
-
Two different subunits, small protein of 28000 (LdTop1S) Leishmania donovani
73000
-
Two different subunits, large protein of 73000 (LdTop1L) Leishmania donovani

Organism

Organism UniProt Comment Textmining
Leishmania donovani
-
-
-

Purification (Commentary)

Purification (Comment) Organism
SDS-PAGE Leishmania donovani

Source Tissue

Source Tissue Comment Organism Textmining

Subunits

Subunits Comment Organism
heterodimer unique heterodimeric DNA topoisomerase IB, consists of a large subunit (LdTop1L), which contains the non-conserved N-terminal end and a phylogenetically conserved core domain, and of a small subunit (LdTop1S) which harbours the C-terminal region with a characteristic tyrosine residue in the active site Leishmania donovani
More important role by part of the N-terminal extension of the small subunit of DNA topoisomerase I, contribute with a main portion of the linker domain of this enzyme Leishmania donovani

Synonyms

Synonyms Comment Organism
DNA topoisomerase I
-
Leishmania donovani
LdTop1
-
Leishmania donovani