Activating Compound | Comment | Organism | Structure |
---|---|---|---|
cAMP | - |
eukaryota | |
additional information | activation involves the activation loop, a polypeptide region outside the active site cleft, which is reversibly phosphorylated at Thr197, dephosphorylation leads to enzyme activation by 2-3fold | eukaryota |
Crystallization (Comment) | Organism |
---|---|
X-ray diffraction structure analysis | eukaryota |
Protein Variants | Comment | Organism |
---|---|---|
T197A | site-directed mutagenesis, highly reduced activity compared to the wild-type enzyme | eukaryota |
T197D | site-directed mutagenesis, reduced activity compared to the wild-type enzyme | eukaryota |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | phosphorylation of the activation loop leads to enzyme inhibition, in which the phosphorylated activation loop acts as an autoinhibitory substrate blocking the nucleotide binding pocket, competition with ATP | eukaryota |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | kinetics of activation and autoinhibition, modeling, pre-steady-state kinetic methods, wild-type and mutant enzymes | eukaryota |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | - |
eukaryota |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + a protein | eukaryota | regulation by reversible phosphorylation, overview | ADP + a phosphoprotein | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
eukaryota | - |
- |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
phosphoprotein | the enzyme is regulated by reversible phosphorylation of the activation loop at Thr197, a polypeptide region outside the active site cleft, the enzyme is inhibited by phosphorylation, which also increases the affinity for ATP by 2fold, and activated by dephosphorylation | eukaryota |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate | activation involves the activation loop, a polypeptide region outside the active site cleft, which is reversibly phosphorylated at Thr197, phosphorylation leads to enzyme inhibition, activation mechanism, overview | eukaryota |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + a protein | - |
eukaryota | ADP + a phosphoprotein | - |
? | |
ATP + a protein | regulation by reversible phosphorylation, overview | eukaryota | ADP + a phosphoprotein | - |
? |
Synonyms | Comment | Organism |
---|---|---|
cAMP-dependent protein kinase | - |
eukaryota |
PKA | - |
eukaryota |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | the binding site is a deep pocket lined by hydrophobic residues, enzyme affinity for ATP is increased 2fold by phosphorylation of the activation loop at Thr197, ATP competes with the phosphorylated activation loop, that acts as an autoinhibitory substrate | eukaryota |