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

Overview

MeSH

  • Animals
  • Base Sequence
  • DNA Primers
  • Humans

MeSH Major

  • Adenylate Cyclase
  • Erythrocytes
  • 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.

publication date

  • 2012

has subject area

  • Adenylate Cyclase
  • Animals
  • Base Sequence
  • DNA Primers
  • Erythrocytes
  • Humans
  • Plasmodium falciparum

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3383692

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0039769

PubMed ID

  • 22761895

Additional Document Info

start page

  • e39769

volume

  • 7

number

  • 6