5t3n: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Sp-2Cl-cAMPS bound to PKAR CBD2== | ==Sp-2Cl-cAMPS bound to PKAR CBD2== | ||
<StructureSection load='5t3n' size='340' side='right' caption='[[5t3n]], [[Resolution|resolution]] 2.40Å' scene=''> | <StructureSection load='5t3n' size='340' side='right'caption='[[5t3n]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5t3n]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Plaf7 Plaf7]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T3N FirstGlance]. <br> | <table><tr><td colspan='2'>[[5t3n]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Plaf7 Plaf7]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T3N FirstGlance]. <br> | ||
| Line 19: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 5t3n" style="background-color:#fffaf0;"></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 == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Plaf7]] | [[Category: Plaf7]] | ||
[[Category: CAMP-dependent protein kinase]] | [[Category: CAMP-dependent protein kinase]] | ||
Revision as of 11:15, 8 January 2020
Sp-2Cl-cAMPS bound to PKAR CBD2Sp-2Cl-cAMPS bound to PKAR CBD2
Structural highlights
Publication 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
|
| ||||||||||||||||||||||