ArticleBiochemical pharmacology2008
Mutational study of the "catalytic tetrad" of DNA topoisomerase IB from the hemoflagellate Leishmania donovani: Role of Asp-353 and Asn-221 in camptothecin resistance.
Article in Biochemical pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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Who cites it
7 citing papers in PubMed, 20 citations in OpenAlex.
- Three different mutations in the DNA topoisomerase 1B in Leishmania infantum contribute to resistance to antitumor drug topotecan.Parasites & vectors · 2021Article
- Trypanosomatids topoisomerase re-visited. New structural findings and role in drug discovery.International journal for parasitology. Drugs and drug resistance · 2014Review
- Article
- Indotecan (LMP400) and AM13-55: two novel indenoisoquinolines show potential for treating visceral leishmaniasis.Antimicrobial agents and chemotherapy · 2012Article
- First total synthesis and antileishmanial activity of (Z)-16-methyl-11-heptadecenoic acid, a new marine fatty acid from the sponge Dragmaxia undata.Chemistry and physics of lipids · 2011Article
- Article
- First total synthesis and antiprotozoal activity of (Z)-17-methyl-13-octadecenoic acid, a new marine fatty acid from the sponge Polymastia penicillus.Chemistry and physics of lipids · 2009Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Leishmania donovani, the causative organism for visceral leishmaniasis, contains a unique bisubunit DNA-topoisomerase IB (LdTopIB). The catalytically active enzyme is a heterodimer constituted by a large subunit (LdTopIL) containing a non-conserved N-terminal end and the phylogenetically conserved core domain, whereas the small subunit (LdTopIS) harbors the C-terminal domain with the characteristic tyrosine residue in the active site. Site-directed mutagenesis was used to substitute the basic amino acid (Arg-314, Lys-352, Arg-410 and His-453) of the LdTopIL subunit by the neutral amino acid alanine. The expression of these mutants in a topoisomerase-free yeast strain produced inactive proteins. Similarly, when the Tyr-222 from small subunit, involved in DNA cleavage, was substituted by Phe no topoisomerase activity was detected in yeast overexpressing extracts. In addition two substitutions involved in camptothecin inhibition were also analyzed. Asp-353 located in the core domain of the large subunit and Asn-221 which heads Tyr-222 in the small subunit, were replaced by Ala and Ser, respectively. These mutants were insensitive to the inhibitor; despite they displayed significant relaxation activity.
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