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Literature summary for 2.7.11.11 extracted from

  • Adams, J.A.
    Kinetic and catalytic mechanisms of protein kinases (2001), Chem. Rev., 101, 2271-2290.
    View publication on PubMed
Search for more literature for 2.7.11.11

Activating Compound

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 (Commentary)

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

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 [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

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/ Products (Substrates)

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

Organism UniProt Comment Textmining
eukaryota
-
-
-

Posttranslational Modification

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

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
a

Substrates and Products (Substrate)

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

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

Synonyms Comment Organism
PKA
-
 eukaryota

Cofactor

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