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AKAP18 contains a phosphoesterase domain that binds AMP.

Authors: Gold, MG  Smith, FD  Scott, JD  Barford, D 
Citation: Gold MG, etal., J Mol Biol. 2008 Feb 1;375(5):1329-43. Epub 2007 Nov 22.
Pubmed: (View Article at PubMed) PMID:18082768
DOI: Full-text: DOI:10.1016/j.jmb.2007.11.037

Protein kinase A anchoring proteins (AKAPs), defined by their capacity to target the cAMP-dependent protein kinase to distinct subcellular locations, function as molecular scaffolds mediating the assembly of multicomponent complexes to integrate and organise multiple signalling events. Despite their central importance in regulating cellular processes, little is known regarding their diverse structures and molecular mechanisms. Here, using bioinformatics and X-ray crystallography, we define a central domain of AKAP18 delta (AKAP18(CD)) as a member of the 2H phosphoesterase family. The domain features two conserved His-x-Thr motifs positioned at the base of a groove located between two lobes related by pseudo 2-fold symmetry. Nucleotide co-crystallisation screening revealed that this groove binds specifically to adenosine 5'-monophosphate (5'AMP) and cytosine 5'-monophosphate (5'CMP), with the affinity constant for AMP in the physiological concentration range. This is the first example of an AKAP capable of binding a small molecule. Our data generate two functional hypotheses for the AKAP18 central domain. It may act as a phosphoesterase, although we did not identify a substrate, or as an AMP sensor with the potential to couple intracellular AMP levels to PKA signalling events.

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RGD Object Information
RGD ID: 2312620
Created: 2009-08-25
Species: All species
Last Modified: 2009-08-25
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.