Linked Life Data

18805675

Source:http://linkedlifedata.com/resource/pubmed/id/18805675

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-12-5
pubmed:abstractText
Resistance to operational drugs is a major barrier to successful antileishmanial chemotherapy that demands development of novel drug intervention strategies based on rational approaches. Model drug resistance phenotypes, such as arsenite resistance used in the current study, facilitate our understanding of the mechanism of drug resistance and assist in identifying new drug target(s). The current study was undertaken to investigate the sensitivity of topoisomerase II (topo II) of arsenite-sensitive (Ld-Wt) and -resistant (Ld-As20) Leishmania donovani to antileishmanial/anti-topo II agents. The effect of antileishmanial/anti-topo II drugs on partially purified topo II enzyme from Ld-Wt and Ld-As20 revealed differential inhibition of topo II decatenation activity for the two strains, with a lower amount of drug required to inhibit activity by 50% in Ld-Wt compared with Ld-As20. Comparison of topo II sequences from both strains indicated a point mutation, R250G, in the ATPase domain of the resistant strain. Furthermore, the Arg-250 of the ATPase domain of topo II was observed to be conserved throughout different species of Leishmania. Variation in the topo II gene sequence between Ld-Wt and Ld-As20 is envisaged to be responsible for the differential behaviour of the enzymes from the two sources.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0924-8579
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
80-5
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Evidence for the presence of R250G mutation at the ATPase domain of topoisomerase II in an arsenite-resistant Leishmania donovani exhibiting a differential drug inhibition profile.
pubmed:affiliation
Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160 062, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't