5t3n | pdb_00005t3n

Sp-2Cl-cAMPS bound to PKAR CBD2

spinqualitylabelsall models 5t3n, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5t3n is a 2 chain structure with sequence from Plaf7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 75G, IOD Related: 5kbf, 5k8s Gene: PKAr, PF3D7_1223100, PFL1110c (PLAF7) Activity: cAMP-dependent protein kinase, with EC number 2.7.11.11 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The ubiquitous second messenger cAMP mediates signal transduction processes in the malarial parasite that regulate host erythrocyte invasion and the proliferation of merozoites. In Plasmodium falciparum the central receptor for cAMP is the single regulatory subunit (R) of Protein kinase A (PKA). To aid the development of compounds that can selectively dysregulate parasite PKA signalling we solved the structure of the PKA regulatory subunit in complex with cAMP and a related analog that displays antimalarial activity: Sp-2Cl-cAMPS. Prior to signalling, PKA-R holds the kinases catalytic subunit (C) in an inactive state by exerting an allosteric inhibitory affect. When two cAMP molecules bind to PKA-R they stabilise a structural conformation that facilitates its dissociation, freeing PKA-C to phosphorylate down-stream substrates such as Apical Membrane Antigen 1. We show that untimely induction of this response with membrane permeable Sp-2Cl-cAMPS blocks parasite proliferation via a PKA-R dependent mechanism. 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 J Biol Chem. 2016 Oct 13. pii: jbc.M116.750174. PMID:27738107 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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