Linked Life Data

15664655

Source:http://linkedlifedata.com/resource/pubmed/id/15664655

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-1-24
pubmed:abstractText
Falcipain-2 and -3 are cysteine proteases of erythrocytic Plasmodium falciparum parasites that appear to function principally as hemoglobinases. To better understand their biological roles, we analyzed the biosynthesis, localization, and processing of these enzymes in cultured parasites. Immunoprecipitation of metabolically labeled proteins indicated that falcipain-2 was synthesized through the trophozoite stage, falcipain-3 appeared in late trophozoites/early schizonts, and both proteases persisted for at least 6 h after synthesis. Falcipain-2 and -3 were localized to the food vacuole, the site of hemoglobin hydrolysis, by immunofluorescence and immunoelectron microscopy. Subcellular fractionation experiments indicated that both enzymes were synthesized as membrane bound proforms that were processed to soluble mature forms, but falcipain-2 was processed to the mature protease much more quickly than was falcipain-3. Cysteine protease inhibitors and brefeldin A, but not aspartic or serine protease inhibitors, blocked the processing of both enzymes, suggesting that falcipain-2 and -3 process by autohydrolysis after exiting the endoplasmic reticulum/Golgi network. However, although all tested cysteine protease inhibitors blocked hemoglobinase activity in the food vacuole, only lipophilic inhibitors (E-64d, Mu-Leu-Hph-VSPh, and ALLN), blocked intracellular processing of falcipain-2 and -3. More hydrophilic inhibitors (E-64 and leupeptin) did not block processing, suggesting that autocatalytic processing of falcipain-2 and -3 occurs in a specific cellular compartment before delivery to the food vacuole. Our results support overlapping but not fully redundant roles for falcipain-2 and -3, which are targeted to the food vacuole and activated sequentially to degrade hemoglobin in erythrocytic parasites.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0166-6851
pubmed:author
pubmed:issnType
Print
pubmed:volume
139
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
205-12
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Biosynthesis, localization, and processing of falcipain cysteine proteases of Plasmodium falciparum.
pubmed:affiliation
Department of Medicine, San Francisco General Hospital, University of California, Box 0811, San Francisco, CA 94143-0811, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't