Related ArticlesTapping the translation potential of cAMP signalling: molecular basis for selectivity in cAMP agonism and antagonism as revealed by NMR.
Biochem Soc Trans. 2014 Apr 1;42(2):302-7
Authors: Boulton S, Akimoto M, Vanschouwen B, Moleschi K, Selvaratnam R, Giri R, Melacini G
Abstract
Eukaryotic CBDs (cAMP-binding domains) control multiple cellular functions (e.g. phosphorylation, guanine exchange and ion channel gating). Hence the manipulation of cAMP-dependent signalling pathways has a high translational potential. However, the ubiquity of eukaryotic CBDs also poses a challenge in terms of selectivity. Before the full translational potential of cAMP signalling can be tapped, it is critical to understand the structural basis for selective cAMP agonism and antagonism. Recent NMR investigations have shown that structurally homologous CBDs respond differently to several CBD ligands and that these unexpected differences arise at the level of either binding (i.e. affinity) or allostery (i.e. modulation of the autoinhibitory equilibria). In the present article, we specifically address how the highly conserved CBD fold binds cAMP with markedly different affinities in PKA (protein kinase A) relative to other eukaryotic cAMP receptors, such as Epac (exchange protein directly activated by cAMP) and HCN (hyperpolarization-activated cyclic-nucleotide-modulated channel). A major emerging determinant of cAMP affinity is hypothesized to be the position of the autoinhibitory equilibrium of the apo-CBD, which appears to vary significantly across different CBDs. These analyses may assist the development of selective CBD effectors that serve as potential drug leads for the treatment of cardiovascular diseases.
[NMR paper] Molecular basis of the PED/PEA15 interaction with the C-terminal fragment of Phospholipase D1 revealed by NMR spectroscopy.
Molecular basis of the PED/PEA15 interaction with the C-terminal fragment of Phospholipase D1 revealed by NMR spectroscopy.
Related Articles Molecular basis of the PED/PEA15 interaction with the C-terminal fragment of Phospholipase D1 revealed by NMR spectroscopy.
Biochim Biophys Acta. 2013 Apr 19;
Authors: Farina B, Doti N, Pirone L, Malgieri G, Pedone EM, Ruvo M, Fattorusso R
Abstract
PED/PEA15 is a small protein involved in many protein-protein interactions that modulates the function of a number of key cellular effectors involved in...
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04-24-2013 09:48 PM
[NMR paper] Bending and adaptability to proteins of the cAMP DNA-responsive element: molecular dy
Bending and adaptability to proteins of the cAMP DNA-responsive element: molecular dynamics contrasted with NMR.
Related Articles Bending and adaptability to proteins of the cAMP DNA-responsive element: molecular dynamics contrasted with NMR.
Biophys J. 2000 Aug;79(2):656-69
Authors: Derreumaux S, Fermandjian S
DNA bending is assumed to play a crucial role during recognition of the cAMP-responsive element (CRE) by transcription factors. However, diverging results have been obtained for the bending direction of the unbound double helix. The...
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Molecular basis of photochromism of a fluorescent protein revealed by direct 13C dete
Molecular basis of photochromism of a fluorescent protein revealed by direct 13C detection under laser illumination
Abstract Dronpa is a green fluorescent protein homologue with a photochromic property. A green laser illumination reversibly converts Dronpa from a green-emissive bright state to a non-emissive dark state, and ultraviolet illumination converts it to the bright state. We have employed solution NMR to understand the underlying molecular mechanism of the photochromism. The detail characterization of Dronpa is hindered as it is metastable in the dark state and spontaneously...
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11-07-2010 02:47 PM
[NMR paper] Solution structure of synthetic peptide inhibitor and substrate of cAMP-dependent pro
Solution structure of synthetic peptide inhibitor and substrate of cAMP-dependent protein kinase. A study by 2D H NMR and molecular dynamics.
Related Articles Solution structure of synthetic peptide inhibitor and substrate of cAMP-dependent protein kinase. A study by 2D H NMR and molecular dynamics.
J Pept Res. 1997 Mar;49(3):210-20
Authors: Padilla A, Hauer JA, Tsigelny I, Parello J, Taylor SS
Peptides derived from the inhibitor of cAMP-dependent protein kinase. PKI, have been studied by 2D 1H NMR techniques. These include the inhibitor...
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08-22-2010 03:31 PM
[NMR paper] Solution structure of synthetic peptide inhibitor and substrate of cAMP-dependent pro
Solution structure of synthetic peptide inhibitor and substrate of cAMP-dependent protein kinase. A study by 2D H NMR and molecular dynamics.
Related Articles Solution structure of synthetic peptide inhibitor and substrate of cAMP-dependent protein kinase. A study by 2D H NMR and molecular dynamics.
J Pept Res. 1997 Mar;49(3):210-20
Authors: Padilla A, Hauer JA, Tsigelny I, Parello J, Taylor SS
Peptides derived from the inhibitor of cAMP-dependent protein kinase. PKI, have been studied by 2D 1H NMR techniques. These include the inhibitor...
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08-22-2010 03:03 PM
[NMR paper] An intrinsic curvature towards the minor groove in the cAMP-responsive element DNA fo
An intrinsic curvature towards the minor groove in the cAMP-responsive element DNA found by combined NMR and molecular modelling studies.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www3.interscience.wiley.com-aboutus-images-wiley_interscience_pubmed_logo_FREE_120x27.gif Related Articles An intrinsic curvature towards the minor groove in the cAMP-responsive element DNA found by combined NMR and molecular modelling studies.
Eur J Biochem. 1999 Feb;259(3):877-86
Authors: Chaoui M, Derreumaux S, Mauffret O, Fermandjian S
The...
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08-21-2010 04:03 PM
[NMR paper] The molecular basis for protein kinase A anchoring revealed by solution NMR.
The molecular basis for protein kinase A anchoring revealed by solution NMR.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.nature.com-images-lo_nsb.gif Related Articles The molecular basis for protein kinase A anchoring revealed by solution NMR.
Nat Struct Biol. 1999 Mar;6(3):222-7
Authors: Newlon MG, Roy M, Morikis D, Hausken ZE, Coghlan V, Scott JD, Jennings PA
Compartmentalization of signal transduction enzymes into signaling complexes is an important mechanism to ensure the specificity of intracellular events. Formation of...
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[Nature network NMR forum] NANUC Boot Camp 2008 (0 replies)
NANUC Boot Camp 2008 (0 replies)
The National High Field NMR Centre at the University of Alberta would like to announce their annual national training course. This year the course will be held at the University of Connecticut Health Center.
Registration forms, brochures, and further information is available at the website
Hopefully the new location will appeal to potential registrants who could not make it Alberta…
Tapping the translation potential of cAMP signalling: molecular basis for selectivity in cAMP agonism and antagonism as revealed by NMR.
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