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Characterization of Plasmodium falciparum adenylyl cyclase-β and its role in erythrocytic stage parasites.

TitleCharacterization of Plasmodium falciparum adenylyl cyclase-β and its role in erythrocytic stage parasites.
Publication TypeJournal Article
Year of Publication2012
AuthorsSalazar E, Bank EM, Ramsey N, Hess KC, Deitsch K, Levin LR, Buck J
JournalPLoS One
Volume7
Issue6
Paginatione39769
Date Published2012
ISSN1932-6203
KeywordsAdenylate Cyclase, Animals, Base Sequence, DNA Primers, Erythrocytes, Humans, Plasmodium falciparum
Abstract

The most severe form of human malaria is caused by the parasite Plasmodium falciparum. The second messenger cAMP has been shown to be important for the parasite's ability to infect the host's liver, but its role during parasite growth inside erythrocytes, the stage responsible for symptomatic malaria, is less clear. The P. falciparum genome encodes two adenylyl cyclases, the enzymes that synthesize cAMP, PfACα and PfACβ. We now show that one of these, PfACβ, plays an important role during the erythrocytic stage of the P. falciparum life cycle. Biochemical characterization of PfACβ revealed a marked pH dependence, and sensitivity to a number of small molecule inhibitors. These inhibitors kill parasites growing inside red blood cells. One particular inhibitor is selective for PfACβ relative to its human ortholog, soluble adenylyl cyclase (sAC); thus, PfACβ represents a potential target for development of safe and effective antimalarial therapeutics.

DOI10.1371/journal.pone.0039769
Alternate JournalPLoS ONE
PubMed ID22761895
PubMed Central IDPMC3383692
Grant ListAI052390 / AI / NIAID NIH HHS / United States
AI064842 / AI / NIAID NIH HHS / United States
R01 AI052390 / AI / NIAID NIH HHS / United States
R01 AI064842 / AI / NIAID NIH HHS / United States
R01 GM062328 / GM / NIGMS NIH HHS / United States

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