The M18 aspartyl aminopeptidase of the human malaria parasite Plasmodium falciparum

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dc.contributor.author Teuscher, F
dc.contributor.author Lowther, J
dc.contributor.author Skinner-Adams, TS
dc.contributor.author Spielmann, T
dc.contributor.author Dixon, MWA
dc.contributor.author Stack, CM
dc.contributor.author Donnelly, S
dc.contributor.author Mucha, A
dc.contributor.author Kafarski, P
dc.contributor.author Vassiliou, S
dc.contributor.author Gardiner, DL
dc.contributor.author Dalton, JP
dc.contributor.author Trenholme, KR
dc.date.accessioned 2009-12-21T02:28:43Z
dc.date.issued 2007-10-19
dc.identifier.citation Journal of Biological Chemistry, 2007, 282 (42), pp. 30817 - 30826
dc.identifier.issn 0021-9258
dc.identifier.other C1 en_US
dc.identifier.uri http://hdl.handle.net/10453/3521
dc.description.abstract A member of the M18 family of aspartyl aminopeptidases is expressed by all intra-erythrocytic stages of the human malaria parasite Plasmodium falciparum (PfM18AAP), with highest expression levels in rings. Functionally active recombinant enzyme, rPfM18AAP, and native enzyme in cytosolic extracts of malaria parasites are 560-kDa octomers that exhibit optimal activity at neutral pH and require the presence of metal ions to maintain enzymatic activity and stability. Like the human aspartyl aminopeptidase, the exopeptidase activity of PfM18AAP is exclusive to N-terminal acidic amino acids, glutamate and aspartate, making this enzyme of particular interest and suggesting that it may function alongside the malaria cytosolic neutral aminopeptidases in the release of amino acids from host hemoglobin-derived peptides. Whereas immunocytochemical studies using transgenic P. falciparum parasites show that PfM18AAP is expressed in the cytosol, immunoblotting experiments revealed that the enzyme is also trafficked out of the parasite into the surrounding parasitophorous vacuole. Antisense-mediated knockdown of PfM18AAP results in a lethal phenotype as a result of significant intracellular damage and validates this enzyme as a target at which novel antimalarial drugs could be directed. Novel phosphinic derivatives of aspartate and glutamate showed modest inhibition of rPfM18AAP but did not inhibit malaria growth in culture. However, we were able to draw valuable observations concerning the structure-activity relationship of these inhibitors that can be employed in future inhibitor optimization studies. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.
dc.language eng
dc.relation.isbasedon 10.1074/jbc.M704938200
dc.title The M18 aspartyl aminopeptidase of the human malaria parasite Plasmodium falciparum
dc.type Journal Article
dc.description.version Published
dc.parent Journal of Biological Chemistry
dc.journal.volume 42
dc.journal.volume 282
dc.journal.number 42 en_US
dc.publocation Bethesda en_US
dc.identifier.startpage 30817 en_US
dc.identifier.endpage 30826 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 995261
dc.personcode 030896
dc.personcode 996591
dc.percentage 100 en_US
dc.classification.name Microbiology en_US
dc.classification.type FOR-08 en_US
dc.location.activity ISI:000250136300050 en_US
dc.location.activity Sacramento, CA
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Faculty of Science
pubs.organisational-group /University of Technology Sydney/Strength - i3
utslib.copyright.status Closed Access
utslib.copyright.date 2015-04-15 12:17:09.805752+10
pubs.consider-herdc true
utslib.collection.history School of Medical and Molecular Sciences (ID: 341)
utslib.collection.history School of Medical and Molecular Sciences (ID: 341)
utslib.collection.history Closed (ID: 3)


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