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Literature summary for 5.6.2.1 extracted from

  • Reguera, R.M.; Redondo, C.M.; Gutierrez de Prado, R.; Perez-Pertejo, Y.; Balana-Fouce, R.
    DNA topoisomerase I from parasitic protozoa: a potential target for chemotherapy (2006), Biochim. Biophys. Acta, 1759, 117-131.
    View publication on PubMed
Search for more literature for 5.6.2.1

Application

Application Comment Organism
drug development DNA topoisomerase I is a potential target for chemotherapy Mammalia
drug development DNA topoisomerase I is a potential target for chemotherapy Homo sapiens
drug development DNA topoisomerase I is a potential target for chemotherapy Leishmania donovani
drug development DNA topoisomerase I is a potential target for chemotherapy Trypanosoma cruzi
drug development DNA topoisomerase I is a potential target for chemotherapy Plasmodium falciparum
drug development DNA topoisomerase I is a potential target for chemotherapy Leishmania major
drug development DNA topoisomerase I is a potential target for chemotherapy Trypanosoma congolense
drug development DNA topoisomerase I is a potential target for chemotherapy Trypanosoma brucei

Protein Variants

Protein Variants Comment Organism
G185R/D325E highly camptothecin-resistant with two substitutions in the core domain of the protein Leishmania donovani

Inhibitors

Inhibitors Comment Organism Structure
5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl D-allopyranoside dideschlororebeccamycin, RM762, indolocarbazole derivative Leishmania donovani
arciriaflavin A RM62, indolocarbazole derivative Leishmania donovani
Berberine a polyheterocyclic class I topoisomerase inhibitor with a structure resembling the intercalant drug benzo[a]acridine. Several berberine analogues tested Leishmania donovani
Berberine is a polyheterocyclic class I topoisomerase inhibitor with a structure resembling the intercalant drug benzo[a]acridine. Several berberine analogues tested Trypanosoma brucei
Berberine is a polyheterocyclic class I topoisomerase inhibitor with a structure resembling the intercalant drug benzo[a]acridine. Several berberine analogues tested Trypanosoma congolense
camptothecin class I topoisomerase poison. Pentacyclic natural alkaloid produced by the plant Camptotheca accuminata Homo sapiens
camptothecin class I topoisomerase poison. Pentacyclic natural alkaloid produced by the plant Camptotheca accuminata Leishmania donovani
camptothecin class I topoisomerase poison. Pentacyclic natural alkaloid producted by the plant Camptotheca accuminata. Camptothecin is cytotoxic for the erythrocytic forms of Plasmodium falciparum Plasmodium falciparum
camptothecin class I topoisomerase poison. Pentacyclic natural alkaloid produced by the plant Camptotheca accuminata Trypanosoma brucei
coralyne derivative of berberine has shown effectively combat Trypanosoma cruzi infection Trypanosoma cruzi
dihydrobetulinic acid DHBA inhibits by preventing enzyme DNA binary complex formation. Inhibits also topoisomerase II Leishmania donovani
diospyrin naphthoquinone derivative Leishmania donovani
irinotecan water soluble derivatives of camptothecin, hardly effective against bloodstream forms of Trypanosoma brucei Trypanosoma brucei
MJ-III-65 indenoisoquinoline analogue Leishmania major
additional information intercalation of indolocarbazole drugs in the DNA molecule is reinforced by the existance of the sugar moiety, which helps to stabilize the insertion complex by binding with the major groove of the ternary duplex DNA. The presence of chlorine atoms disminishes topoisomerase I inhibition Leishmania donovani
rebeccamycin REB, indolocarbazole derivative Leishmania donovani
rebeccamycin
-
 Trypanosoma brucei
topotecan hydrochloride water soluble derivatives of camptothecin, hardly effective against bloodstream forms of Trypanosoma brucei Trypanosoma brucei

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
28000
-
 small subunit LdTOPIB, on chromosome 4, encoding for a 262-amino acid polypeptide. The small subunit contains SKXXY motif placed at the C-terminal domain of all type I DNA topoisomerases, which conserves the tyrosine residue that plays a role in DNA cleavage Leishmania donovani
73000
-
 large subunit LdTOPIA, on chromosome 34, encoding for a 636-amino acid polypeptide Leishmania donovani
91000
-
-
 Mammalia
91000
-
-
 Homo sapiens
104000
-
-
 Plasmodium falciparum

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Leishmania donovani
-
-
-
Leishmania major
-
-
-
Mammalia
-
-
-
Plasmodium falciparum
-
-
-
Trypanosoma brucei Q581U8
-
-
Trypanosoma congolense
-
-
-
Trypanosoma cruzi
-
-
-

Subunits

Subunits Comment Organism
heterodimer presence of two separate genes encoding for the core and catalytic domains, indicating that this singular feature is common to all trypanosomatids Trypanosoma cruzi
heterodimer the genes encoding each protein subunit are located on different chromosomes Leishmania donovani
monomer 765 amino acids. All type IB topoisomerases contain a conserved SKXXY signature in the region in which a tyrosine residue (Tyr-723 in the human topoisomeraseI) is the DNA-cleaving amino acid Homo sapiens
monomer 765 amino acids. All type IB topoisomerases contain a conserved SKXXY signature in the regionin which a tyrosine residue is the DNA-cleaving amino acid Mammalia
monomer Three structural domains, N-terminus domain (134 amino acids) poorly conserved, a 500 amino acid length block of conserved amino acids with high homology to the core domain of the human protein, the C-terminal domain is smaller than the hosts' but conserves the active tyrosine at position 798 which makes the enzyme fully active Plasmodium falciparum
More multimeric status of Trypanosoma brucei TopI. Molecular mass determination by gel filtration chromatography suggests that the native enzyme might exist as a tetrameric active A2B2 form or two heterodimers would facilitate the binding at the helical crossover points of DNA Trypanosoma brucei
More regulation of DNA topoisomerase I, different expression patterns described in the distinct life cycle stages of Plasmodium falciparum. An indirect evidence of potential post-translational mechanisms which could operate on Plasmodium topoisomerases at different stages of its life cycle Plasmodium falciparum
More relaxation activity of human TopI by adding to the core domain a series of peptides containing the C-terminal domain in the presence of DNA. Reinforced by using a two-hybrid expression system, identified proteins containing part of the linker and the C-terminal domain that supplemented the catalytic core of Saccharomyces cerevisiae topoisomerase I Homo sapiens

Synonyms

Synonyms Comment Organism
DNA topoisomerase I
-
 Mammalia
DNA topoisomerase I
-
 Homo sapiens
DNA topoisomerase I
-
 Leishmania donovani
DNA topoisomerase I
-
 Trypanosoma cruzi
DNA topoisomerase I
-
 Plasmodium falciparum
DNA topoisomerase I
-
 Leishmania major
DNA topoisomerase I
-
 Trypanosoma congolense
DNA topoisomerase I
-
 Trypanosoma brucei
PfTopI
-
 Plasmodium falciparum
TopI
-
 Homo sapiens

pI Value

Organism Comment pI Value Maximum pI Value
Trypanosoma brucei overall charge difference observed, proposed that the protein regions bearing these differences may contribute to establishing ionic interactions that hold the subunits together
-
 additional information
Trypanosoma brucei small subunit
-
 5.21
Trypanosoma brucei large subunit
-
 9.47