Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Application of small cardioactive peptide (SCP) or stimulation of motorneuron B15 increases the level of activated cAMP-dependent protein kinase (cAPK) in the ARC muscle. SCP application also appears to induce a translocation of cAPK between different subcellular compartments of the ARC muscle and this translocation is also induced by cAMP addition to muscle homogenates. These results suggest that the actions of SCP in the Aplysia ARC neuromuscular system are mediated via the cAPK signal transduction pathway.
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PMID:SCP application or B15 stimulation activates cAPK in the ARC muscle of Aplysia. 782 Jun 39

The crystal structure of a complex of the catalytic subunit (type alpha) of cAMP-dependent protein kinase (PKA C alpha) with ARC-type inhibitor (ARC-1034), the presumed lead scaffold of previously reported adenosine-oligo-arginine conjugate-based (ARC-type) inhibitors, was solved. Structural elements important for interaction with the kinase were established with specifically modified derivatives of the lead compound. On the basis of this knowledge, a new generation of inhibitors, conjugates of adenosine-4'-dehydroxymethyl-4'-carboxylic acid moiety and oligo(D-arginine), was developed with inhibitory constants well into the subnanomolar range. The structural determinants of selectivity of the new compounds were established in assays with ROCK-II and PKBgamma.
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PMID:Structural analysis of ARC-type inhibitor (ARC-1034) binding to protein kinase A catalytic subunit and rational design of bisubstrate analogue inhibitors of basophilic protein kinases. 1914 65

The acknowledged potential of small-molecule therapeutics targeting disease-related protein-protein interactions (PPIs) has promoted active research in this field. The strategy of using small molecule inhibitors (SMIs) to fight strong (tight-binding) PPIs tends to fall short due to the flat and wide interfaces of PPIs. Here we propose a biligand approach for disruption of strong PPIs. The potential of this approach was realized for disruption of the tight-binding (KD = 100 pM) tetrameric holoenzyme of cAMP-dependent protein kinase (PKA). Supported by X-ray analysis of cocrystals, bifunctional inhibitors (ARC-inhibitors) were constructed that simultaneously associated with both the ATP-pocket and the PPI interface area of the catalytic subunit of PKA (PKAc). Bifunctional inhibitor ARC-1411, possessing a KD value of 3 pM toward PKAc, induced the dissociation of the PKA holoenzyme with a low-nanomolar IC50, whereas the ATP-competitive inhibitor H89 bound to the PKA holoenzyme without disruption of the protein tetramer.
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PMID:Bifunctional Ligands for Inhibition of Tight-Binding Protein-Protein Interactions. 2738 35