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1.
Artigo em Inglês | IMSEAR | ID: sea-18794

RESUMO

Protozoan parasites of the order Kinetoplastida cause severe diseases primarily in the tropical and subtropical areas. The enormous development of molecular and cellular biology in recent times have provided opportunities for discovering newer molecular targets for drug designing, which now form a rational basis for the development of improved anti-parasitic therapy. DNA topoisomerases play a key role in cellular processes affecting the topology and organization of intracellular DNA. Recently, emergence of the bi-subunit topoisomerase I in the kinetoplastid family has brought a new twist in topoisomerase research related to evolution, functional conservation and as a potential target that can be exploited in drug designing and development of new intervention strategies. This review summarizes the biology of kinetoplastid topoisomerases, which are the key molecular targets in antileishmanial chemotherapy.


Assuntos
Animais , DNA/química , DNA Topoisomerases/química , DNA de Cinetoplasto/metabolismo , Humanos , Imuno-Histoquímica , Leishmania donovani/enzimologia , Leishmaniose/terapia , Microscopia Eletrônica , Estrutura Terciária de Proteína , Especificidade da Espécie , Trypanosoma
2.
Indian J Biochem Biophys ; 1993 Oct; 30(5): 257-63
Artigo em Inglês | IMSEAR | ID: sea-27867

RESUMO

A type 1 DNA topoisomerase has been purified from the nuclei of the kinetoplast hemoflagellate Leishmania donovani using polyethylene glycol fractionation and chromatography on hydroxylapatite, phosphocellulose and phenylsepharose column. The relaxation activity is ATP independent. Mg2+ is an essential cofactor for the reaction with an optimum at 10 mM. Mg2+ can be substituted by Mn2+ at 5 mM concentration. The relaxation reaction exhibits a salt optimum at 100 mM KCl. The enzyme can not remove supercoils from positive superhelical DNAs nor can induce supercoiling of relaxed DNAs. The topoisomerase activity is associated with a polypeptide of molecular weight about 67 kDa as shown by sephacryl-S200 gel filtration and by electrophoresis on sodium dodecyl sulphate-polyacrylamide gels.


Assuntos
Animais , Núcleo Celular/enzimologia , Cromatografia , Cromatografia por Troca Iônica , DNA Topoisomerases Tipo I/isolamento & purificação , DNA de Cinetoplasto/metabolismo , Durapatita , Cinética , Leishmania donovani/enzimologia , Polietilenoglicóis
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