5kbf: Difference between revisions
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The | ==cAMP bound PfPKA-R (141-441)== | ||
<StructureSection load='5kbf' size='340' side='right'caption='[[5kbf]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5kbf]] 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=5KBF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KBF 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]] 2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CMP:ADENOSINE-3,5-CYCLIC-MONOPHOSPHATE'>CMP</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=5kbf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kbf OCA], [https://pdbe.org/5kbf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kbf RCSB], [https://www.ebi.ac.uk/pdbsum/5kbf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kbf 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5kbf" 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: Crabb BS]] | |||
[[Category: Gilson PR]] | |||
[[Category: Littler DR]] | |||
[[Category: Rossjohn JJ]] | |||
Latest revision as of 12:57, 27 September 2023
cAMP bound PfPKA-R (141-441)cAMP bound PfPKA-R (141-441)
Structural highlights
FunctionPublication Abstract from PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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