Characterization of Leishmania chagasi DNA topoisomerase II: a potential chemotherapeutic target.
DNA topoisomerase II (topo II), an enzyme essential for cellular replication, is an eminent target for antimicrobial therapy against Leishmania chagasi, the major cause of visceral leishmaniasis in Latin America. The complete L. chagasi (Lch) TOP2 gene, encoding L. chagasi topo II, was isolated from genomic DNA using the polymerase chain reaction. The LchTOP2 gene revealed an open reading frame (ORF) of 3,711 base pairs predicting a protein with 1,236 amino acids and an estimated molecular weight of 140 kDA. The L. chagasi topo II sequence had high identity with the L. donovani topo II (98.8%) and L. infantum topo II (98.7%), followed by Crithidia fasciculata topo II (84.4%), Trypanosoma cruzi topo II (67.6%) and Trypanosoma brucei topo II (66.6%). Lch topo II had low identity with the human homologs htopo II alpha (26.3%) and htopo II beta (26.4%). Differences between L. chagasi TOP2 and human TOP2 genes suggest that leishmanial topo II is a potential target for the development of new antileishmanial agents.
De Sousa
Jacira M A
JM
Department of Biochemistry, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
Lareau
Susan M
SM
Pearson
Richard D
RD
Carvalho
Edgar M
EM
Mann
Barbara J
BJ
Jeronimo
Selma M B
SM
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D001483:Base Sequence; D015139:Blotting, Southern; D003001:Cloning, Molecular; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D006801:Humans; D018314:Leishmania infantum / Q000187:drug effects* / Q000235:genetics*; D007898:Leishmaniasis, Visceral / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D008969:Molecular Sequence Data; D010597:Pharmacogenetics; D016133:Polymerase Chain Reaction / Q000379:methods; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA
D000981:Antiprotozoal Agents; D004250:DNA Topoisomerases, Type II