Activating Compound | Comment | Organism | Structure |
---|---|---|---|
cAMP | binds to the 2 catalytic subunits and activates via dissociation of the regulatory dimer | 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 2-3fold activation | eukaryota |
Crystallization (Comment) | Organism |
---|---|
X-ray diffraction structure analysis of the catalytic subunits and the regulatory R2 dimer, enzyme cocrystallized with ATP and a peptide inhibitor | eukaryota |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
ADP | noncompetitive inhibition with respect to ATP | eukaryota | |
guanethidine | noncompetitive inhibiting serine peptide analogue with respect to ATP | eukaryota | |
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 | |
peptide inhibitor PKI | - |
eukaryota |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | kinetics, random kinetic mechanism with kemptide as substrate, reaction kinetic can be influenced by the sort of substrate, pre-steady-state kinetics, slow structural changes during reaction | eukaryota |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Cd2+ | can partially substitue Mg2+ | eukaryota | |
Co2+ | can partially substitue Mg2+ | eukaryota | |
Mg2+ | dependent on, chelates the beta- and gamma-phosphate of ATP, Mg2+ is the physiologic metal ion, other divalent cations are able to support nucleotide binding, but only Mn2+, Co2+, and Cd2+ can substitute Mg2+ in supporting the catalytic activity | eukaryota | |
Mn2+ | can partially substitue Mg2+ | eukaryota |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + a protein | eukaryota | regulation of the enzyme involves reversible phosphorylation at the activation loop, and associative or dissociative mechanisms | ADP + a phosphoprotein | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
eukaryota | - |
- |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
phosphoprotein | regulation by phosphorylation at Thr197 of the activation loop, enhances ATP binding and phosphotransfer, but only slightly the substrate binding | eukaryota |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate | random kinetic mechanism, active site structure with key residues E91, K72, N171, K168, the general base catalyst D166, and essential catalytic D184, overview, reaction mechanism | eukaryota |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + a protein | regulation of the enzyme involves reversible phosphorylation at the activation loop, and associative or dissociative mechanisms | eukaryota | ADP + a phosphoprotein | - |
? | |
ATP + a protein | the enzyme phosphorylates the peptide substrate LRRASLG | eukaryota | ADP + a phosphoprotein | - |
? | |
ATP + kemptide | - |
eukaryota | ADP + phospho-kemptide | - |
? | |
additional information | poor activity on free amino acids, consensus sequence of PKA is R-RXS/T hyd | eukaryota | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | structure modeling, structural elements, overview | eukaryota |
tetramer | a heterotetramer composed of a regulatory dimer and 2 catalytic subunits, the tetramer is inactive, dissociation of the tetramer occurs during activation and cAMP binding | eukaryota |
Synonyms | Comment | Organism |
---|---|---|
PKA | - |
eukaryota |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | dependent on, 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 |