title: Characterization of Plasmodium falciparum adenylyl cyclase-β and its role in erythrocytic stage parasites.
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.
authors: Tri-Institutional MD-PhD Program, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, New York, United States of America.
authors: Eric
authors: E
authors: Salazar
authors: Erin M
authors: EM
authors: Bank
authors: Nicole
authors: N
authors: Ramsey
authors: Kenneth C
authors: KC
authors: Hess
authors: Kirk W
authors: KW
authors: Deitsch
authors: Lonny R
authors: LR
authors: Levin
authors: Jochen
authors: J
authors: Buck
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics
chemical_list: D017931:DNA Primers; D000262:Adenylyl Cyclases