Linked Life Data

15225307

Source:http://linkedlifedata.com/resource/pubmed/id/15225307

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-6-30
pubmed:databankReference
pubmed:abstractText
Lipoic acid is an essential cofactor of alpha-keto acid dehydrogenase complexes (KADHCs). This study shows that Plasmodium falciparum possesses two distinct lipoylation pathways that are found in separate subcellular localizations. Lipoic acid synthesis comprising lipoic acid synthase and lipoyl-ACP:protein N-lipoyl transferase is present in the parasite's apicoplast, whereas the second pathway consisting of lipoic acid protein ligase is located in the parasite's mitochondrion. The two localizations were established by overexpressing green fluorescent protein fusions of the N-terminal sequences of lipoic acid synthase and lipoic acid protein ligase in intraerythrocytic stages of P. falciparum. Northern and Western blot analyses revealed that the genes/proteins encoding lipoic acid synthase, lipoyl-ACP:protein N-lipoyl transferase and lipoic acid protein ligase are expressed maximally in the early and late stages of P. falciparum erythrocytic development. The functionality of the three proteins was proven by complementation of bacteria deficient in lipA and lipB. Our results show that P. falciparum possesses two independent pathways, with different locations, responsible for the post-translational modification of KADHCs. Both pathways fundamentally differ from those in the human host. As KADHCs provide metabolites that are required for essential biosynthetic processes such as fatty acid biosynthesis and haem biosynthesis, the two lipoylation pathways of P. falciparum might be attractive therapeutic targets against malaria.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0950-382X
pubmed:author
pubmed:issnType
Print
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
103-13
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
The human malaria parasite Plasmodium falciparum has distinct organelle-specific lipoylation pathways.
pubmed:affiliation
Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, WTB/MSI Complex, Dundee DD1 5EH, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't