Overexpression of leucyl aminopeptidase in Plasmodium falciparum parasites. Target for the antimalarial activity of bestatin.

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dc.contributor.author Gardiner, DL
dc.contributor.author Trenholme, KR
dc.contributor.author Skinner-Adams, TS
dc.contributor.author Stack, CM
dc.contributor.author Dalton, JP
dc.date.accessioned 2009-12-21T02:28:52Z
dc.date.issued 2006-01
dc.identifier.citation The Journal of biological chemistry, 2006, 281 (3), pp. 1741 - 1745
dc.identifier.issn 0021-9258
dc.identifier.other C1 en_US
dc.identifier.uri http://hdl.handle.net/10453/3565
dc.description.abstract Malaria aminopeptidases are important in the generation and regulation of free amino acids that are used in protein anabolism and for maintaining osmotic stability within the infected erythrocyte. The intraerythrocytic development of malaria parasites is blocked when the activity of aminopeptidases is specifically inhibited by reagents such as bestatin. One of the major aminopeptidases of malaria parasites is a leucyl aminopeptidase of the M17 family. We reasoned that, when this enzyme was the target of bestatin inhibition, its overexpression in malaria cells would lead to a reduced sensitivity to the inhibitor. To address this supposition, transgenic Plasmodium falciparum parasites overexpressing the leucyl aminopeptidase were generated by transfection with a plasmid that housed the full-length gene. Transgenic parasites expressed a 65-kDa protein close to the predicted molecule size of 67.831 kDa for the introduced leucyl aminopeptidase, and immunofluorescence studies localized the protein to the cytosol, the location of the native enzyme. The product of the transgene was shown to be functionally active with cytosolic extracts of transgenic parasites exhibiting twice the leucyl aminopeptidase activity compared with wild-type parasites. In vitro inhibitor sensitivity assays demonstrated that the transgenic parasites were more resistant to bestatin (EC50 64 microM) compared with the parent parasites (EC50 25 microM). Overexpression of genes in malaria parasites would have general application in the identification and validation of targets for antimalarial drugs.
dc.format Print-Electronic
dc.language eng
dc.relation.isbasedon 10.1074/jbc.m508955200
dc.title Overexpression of leucyl aminopeptidase in Plasmodium falciparum parasites. Target for the antimalarial activity of bestatin.
dc.type Journal Article
dc.parent The Journal of biological chemistry
dc.journal.volume 3
dc.journal.volume 281
dc.journal.number 3 en_US
dc.publocation Bethesda, USA en_US
dc.publocation Hershey, PA & London, UK
dc.identifier.startpage 1741 en_US
dc.identifier.endpage 1745 en_US
dc.cauo.name SCI.Medical and Molecular Biosciences en_US
dc.conference Verified OK en_US
dc.for 0605 Microbiology
dc.personcode 995262
dc.personcode 030896
dc.percentage 100 en_US
dc.classification.name Microbiology en_US
dc.classification.type FOR-08 en_US
dc.edition 1
dc.description.keywords Animals
dc.description.keywords Animals, Genetically Modified
dc.description.keywords Plasmodium falciparum
dc.description.keywords Leucyl Aminopeptidase
dc.description.keywords DNA Primers
dc.description.keywords Protozoan Proteins
dc.description.keywords Recombinant Proteins
dc.description.keywords Protease Inhibitors
dc.description.keywords Transfection
dc.description.keywords Base Sequence
dc.description.keywords Kinetics
dc.description.keywords Exons
dc.description.keywords Leucine
dc.description.keywords Antimalarials
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Faculty of Science
utslib.copyright.status Closed Access
utslib.copyright.date 2015-04-15 12:17:09.805752+10
pubs.consider-herdc true
utslib.collection.history Closed (ID: 3)

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