Characterization of Plasmodium falciparum Adenylyl Cyclase-β and its role in Erythrocytic stage parasites

Eric Salazar, Erin M. Bank, Nicole Ramsey, Kenneth C. Hess, Kirk W. Deitsch, Lonny R. Levin, Jochen Buck

Research output: Contribution to journalArticle

17 Scopus citations

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.

Original languageEnglish (US)
Article numbere39769
JournalPLoS ONE
Volume7
Issue number6
DOIs
StatePublished - Jun 26 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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