Journal article
Vacuolar type H+ pumping pyrophosphatases of parasitic protozoa
International journal for parasitology, v 32(1), pp 1-14
Jan 2002
PMID: 11796117
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Trans-membrane proton pumping is responsible for a myriad of physiological processes including the generation of proton motive force that drives bioenergetics. Among the various proton pumping enzymes, vacuolar pyrophosphatases (V-PPases) form a distinct class of proton pumps, which are characterised by their ability to translocate protons across a membrane by using the potential energy released by hydrolysis of the phosphoanhydride bond of inorganic pyrophosphate. Until recently, V-PPases were known to be the purview of only plant vacuoles and plasma membranes of phototrophic bacteria. Recent discoveries of V-PPases in kinetoplastid and apicomplexan parasites, however, have expanded our view of the evolutionary reach of these enzymes. The lack of V-PPases in the vertebrate hosts of these parasites makes them potentially excellent targets for developing broad-spectrum antiparasitic agents. This review surveys the current understanding of V-PPases in parasitic protozoa with an emphasis on malaria parasites. Topological predictions suggest remarkable similarity of the parasite enzymes to their plant homologues with 15-16 membrane spanning domains and conserved sequences shown to constitute critical catalytic residues. Remarkably, malaria parasites have been shown to possess two V-PPase genes, one is an apparent orthologue of the canonical plant enzyme, whereas the other is a more distantly related paralogue with homology to a recently identified new class of K+-insensitive plant V-PPases. V-PPases appear to localise both to the plasma membrane and cytoplasmic organelles believed to be acidocalcisomes or polyphosphate bodies. Gene transfer experiments suggest that one of the malarial V-PPases is predominantly localised to the surface of intraerythrocytic parasites. We suggest a model in which V-PPase localised to the malaria parasite plasma membrane may serve as an electrogenic pump utilising pyrophosphate as an energy source, thus sparing the more precious ATP. Searching for V-PPase inhibitors could prove fruitful as a novel means of antiparasitic chemotherapy.
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Details
- Title
- Vacuolar type H+ pumping pyrophosphatases of parasitic protozoa
- Creators
- Michael T McIntosh - Drexel UniversityAkhil B Vaidya - Drexel UniversityAshok B Vaidya - Microbiology and Immunology
- Publication Details
- International journal for parasitology, v 32(1), pp 1-14
- Publisher
- Elsevier
- Grant note
- R01 AI028398 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000173758000001
- Scopus ID
- 2-s2.0-0036160199
- Other Identifier
- 991019169804504721
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InCites Highlights
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Parasitology