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Disrupting the Allosteric Interaction between the Plasmodium falciparum cAMP-dependent Kinase and Its Regulatory Subunit.

Littler DR, Bullen HE, Harvey KL, Beddoe T, Crabb BS, Rossjohn J, Gilson PR

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  • Journal The Journal of biological chemistry

  • Published 13 Oct 2016

  • Volume 291

  • ISSUE 49

  • Pagination 25375-25386

  • DOI 10.1074/jbc.M116.750174

Abstract

)-2-Cl-cAMPS. Prior to signaling, PKA-R holds the kinase's catalytic subunit (C) in an inactive state by exerting an allosteric inhibitory effect. When two cAMP molecules bind to PKA-R, they stabilize a structural conformation that facilitates its dissociation, freeing PKA-C to phosphorylate downstream substrates such as apical membrane antigen 1. Although PKA activity was known to be necessary for erythrocytic proliferation, we show that uncontrolled induction of PKA activity using membrane-permeable agonists is equally disruptive to growth.