View source for 5t3n


==Sp-2Cl-cAMPS bound to PKAR CBD2==
<StructureSection load='5t3n' size='340' side='right'caption='[[5t3n]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5t3n]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T3N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5T3N FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=75G:(2S,4AR,6R,7R,7AS)-6-(6-AMINO-2-CHLORO-9H-PURIN-9-YL)-7-HYDROXY-2-SULFANYLTETRAHYDRO-2H,4H-2LAMBDA~5~-FURO[3,2-D][1,3,2]DIOXAPHOSPHININ-2-ONE'>75G</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5t3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t3n OCA], [https://pdbe.org/5t3n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5t3n RCSB], [https://www.ebi.ac.uk/pdbsum/5t3n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5t3n ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q7KQK0_PLAF7 Q7KQK0_PLAF7] 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:27738107</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5t3n" style="background-color:#fffaf0;"></div>

==See Also==
*[[CAMP-dependent protein kinase 3D structures|CAMP-dependent protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum 3D7]]
[[Category: Gilson P]]
[[Category: Littler DR]]