Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary extracted from

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

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.7.11.11 cAMP binds to the 2 catalytic subunits and activates via dissociation of the regulatory dimer eukaryota
2.7.11.11 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
2.7.11.22 cyclin A cdk2 is dependent on, required as activating subunit, complexes with cdk2 eukaryota
2.7.11.24 additional information activation mechanism, phosphorylation/activation of ERK1 and ERK2 by the MAPK kinase-1 eukaryota

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.7.10.2
-
 eukaryota
2.7.11.11 X-ray diffraction structure analysis of the catalytic subunits and the regulatory R2 dimer, enzyme cocrystallized with ATP and a peptide inhibitor eukaryota
2.7.11.22 cdk2, X-ray diffraction structure analysis eukaryota
2.7.11.24 ERK2, X-ray diffraction structure analysis eukaryota

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.11.11 ADP noncompetitive inhibition with respect to ATP eukaryota
2.7.11.11 guanethidine noncompetitive inhibiting serine peptide analogue with respect to ATP eukaryota
2.7.11.11 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
2.7.11.11 peptide inhibitor PKI
-
 eukaryota

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.7.10.2 additional information
-
 additional information c-Src, Csk: random kinetic mechanism, reaction kinetic can be influenced by the sort of substrate, high affinity for ADP eukaryota
2.7.11.11 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
2.7.11.19 additional information
-
 additional information random kinetic mechanism, reaction order can be influenced by the sort of substrate eukaryota
2.7.11.24 additional information
-
 additional information p38alpha: kinetic mechanism, reaction kinetics can be influenced by the sort of substrate eukaryota

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.7.10.2 soluble
-
 eukaryota
-
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.10.2 Cd2+ can partially substitue Mg2+ eukaryota
2.7.10.2 Co2+ can partially substitue Mg2+ eukaryota
2.7.10.2 Mg2+ dependent on, 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
2.7.10.2 Mn2+ can partially substitue Mg2+ eukaryota
2.7.11.11 Cd2+ can partially substitue Mg2+ eukaryota
2.7.11.11 Co2+ can partially substitue Mg2+ eukaryota
2.7.11.11 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
2.7.11.11 Mn2+ can partially substitue Mg2+ eukaryota
2.7.11.19 Cd2+ can partially substitue Mg2+ eukaryota
2.7.11.19 Co2+ can partially substitue Mg2+ eukaryota
2.7.11.19 Mg2+ dependent on, 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
2.7.11.19 Mn2+ can partially substitue Mg2+ eukaryota
2.7.11.22 Cd2+ can partially substitue Mg2+ eukaryota
2.7.11.22 Co2+ can partially substitue Mg2+ eukaryota
2.7.11.22 Mg2+ dependent on, 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
2.7.11.22 Mn2+ can partially substitue Mg2+ eukaryota
2.7.11.24 Cd2+ can partially substitue Mg2+ eukaryota
2.7.11.24 Co2+ can partially substitue Mg2+ eukaryota
2.7.11.24 Mg2+ dependent on, 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
2.7.11.24 Mn2+ can partially substitue Mg2+ eukaryota
2.7.12.2 Cd2+ can partially substitue Mg2+ eukaryota
2.7.12.2 Co2+ can partially substitue Mg2+ eukaryota
2.7.12.2 Mg2+ dependent on, 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
2.7.12.2 Mn2+ can partially substitue Mg2+ eukaryota

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.10.2 ATP + a protein eukaryota
-
 ADP + a phosphoprotein
-
 ?
2.7.11.11 ATP + a protein eukaryota regulation of the enzyme involves reversible phosphorylation at the activation loop, and associative or dissociative mechanisms ADP + a phosphoprotein
-
 ?
2.7.11.19 ATP + phosphorylase b eukaryota
-
 ADP + phosphorylase a
-
 ?
2.7.11.22 ATP + a protein eukaryota
-
 ADP + a phosphoprotein
-
 ?
2.7.11.24 ATP + a protein eukaryota
-
 ADP + a phosphoprotein
-
 ?
2.7.12.2 ATP + a protein eukaryota
-
 ADP + a phosphoprotein
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.10.2 eukaryota
-
-
-
2.7.11.11 eukaryota
-
-
-
2.7.11.19 eukaryota
-
-
-
2.7.11.22 eukaryota
-
-
-
2.7.11.24 eukaryota
-
-
-
2.7.12.2 eukaryota
-
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
2.7.10.2 phosphoprotein regulation by phosphorylation of the activation loop, decreases ATP binding and substrate binding, enhances the phosphotransfer rate eukaryota
2.7.11.11 phosphoprotein regulation by phosphorylation at Thr197 of the activation loop, enhances ATP binding and phosphotransfer, but only slightly the substrate binding eukaryota
2.7.11.22 phosphoprotein regulation by phosphorylation of the activation loop, does not affect ATP binding, but enhances the phosphotransfer rate and the substrate binding eukaryota
2.7.11.24 phosphoprotein regulation by phosphorylation of the activation loop, increases substrate and ATP binding as well as the phosphotransfer rate, phosphorylation/activation of ERK1 and ERK2 by the MAPK kinase-1 eukaryota

Reaction

EC Number Reaction Comment Organism Reaction ID
2.7.10.2 ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate reaction mechanism eukaryota
a
2.7.11.11 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
2.7.11.22 ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate reaction mechanism eukaryota
a
2.7.11.24 ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate reaction mechanism eukaryota
a

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.10.2 ATP + a protein
-
 eukaryota ADP + a phosphoprotein
-
 ?
2.7.10.2 ATP + a protein PhK phosphorylates e.g. the protein substrate GPb, v-Fps phosphorylates e.g. the peptide substrate EAEIYEAEI, Csk phosphorylates e.g. the substrate poly-Glu4-Tyr eukaryota ADP + a phosphoprotein
-
 ?
2.7.10.2 additional information poor activity on free amino acids, consensus sequence of c-Src is E-EIYE/G-XF, that of v-Fps is E-IYE-XI/V, and that of Csk is IYM-F-F-F, specificity overview eukaryota ?
-
 ?
2.7.11.11 ATP + a protein regulation of the enzyme involves reversible phosphorylation at the activation loop, and associative or dissociative mechanisms eukaryota ADP + a phosphoprotein
-
 ?
2.7.11.11 ATP + a protein the enzyme phosphorylates the peptide substrate LRRASLG eukaryota ADP + a phosphoprotein
-
 ?
2.7.11.11 ATP + kemptide
-
 eukaryota ADP + phospho-kemptide
-
 ?
2.7.11.11 additional information poor activity on free amino acids, consensus sequence of PKA is R-RXS/T hyd eukaryota ?
-
 ?
2.7.11.19 ATP + a protein
-
 eukaryota ADP + a phosphoprotein
-
 ?
2.7.11.19 ATP + phosphorylase b
-
 eukaryota ADP + phosphorylase a
-
 ?
2.7.11.19 additional information poor activity on free amino acids, consensus sequence of PhK is R-XXS/TF-F eukaryota ?
-
 ?
2.7.11.22 ATP + a protein
-
 eukaryota ADP + a phosphoprotein
-
 ?
2.7.11.22 ATP + a protein cdk2-cyclin A phosphorylates e.g. protein substrate p107 and peptide substrate PKTPKKAKKL, requiring a small hydrophobic patch RXL, known as a recruitment peptide eukaryota ADP + a phosphoprotein
-
 ?
2.7.11.22 additional information poor activity on free amino acids, consensus sequence of cdk2 is S/TP-XR/K eukaryota ?
-
 ?
2.7.11.24 ATP + a protein
-
 eukaryota ADP + a phosphoprotein
-
 ?
2.7.11.24 ATP + a protein ERK2 phosphorylates MBP, p38 phosphorylates the protein substrate MAPKAP2 and the peptide substrate KRELVEPLTPSGEAPNQALLR, other substrates of MAPK are transcription factors, such as c-Jun, ATF-2, and MEF2A eukaryota ADP + a phosphoprotein
-
 ?
2.7.11.24 additional information poor activity on free amino acids, consensus sequence of ERK2 is P-XS/TP, substrate specificity and recognition elements, e.g. PXTP, the activity on the protein substrate is much higher compared to a 14-residue peptide containing the phosphorylation site eukaryota ?
-
 ?
2.7.12.2 ATP + a protein
-
 eukaryota ADP + a phosphoprotein
-
 ?
2.7.12.2 ATP + a protein MKK1 phosphorylates and activates the MAP kinases ERK1 and ERK2 eukaryota ADP + a phosphoprotein
-
 ?

Subunits

EC Number Subunits Comment Organism
2.7.10.2 More the enzyme consists of a kinase core and 2 noncatalytic portions SH2 and SH3 eukaryota
2.7.11.11 More structure modeling, structural elements, overview eukaryota
2.7.11.11 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
2.7.11.19 More phosphorylase kinase is a multisubunit protein kinase with molecular weight above 1000000 Da eukaryota
2.7.11.22 More the enzyme requires a cyclin as activating subunit eukaryota

Synonyms

EC Number Synonyms Comment Organism
2.7.10.2 C-SRC
-
 eukaryota
2.7.10.2 C-terminal Src kinase
-
 eukaryota
2.7.10.2 cellular form of the transforming agent of Rous sarcoma virus
-
 eukaryota
2.7.10.2 Csk
-
 eukaryota
2.7.10.2 transforming agent of Fujinami sarcoma virus
-
 eukaryota
2.7.10.2 v-Fps
-
 eukaryota
2.7.11.11 PKA
-
 eukaryota
2.7.11.19 PhK
-
 eukaryota
2.7.11.22 CDK2
-
 eukaryota
2.7.11.22 cyclin-dependent kinase-2
-
 eukaryota
2.7.11.24 ERK1
-
 eukaryota
2.7.11.24 ERK2
-
 eukaryota
2.7.11.24 extracellular-regulated kinase-1
-
 eukaryota
2.7.11.24 extracellular-regulated kinase-2
-
 eukaryota
2.7.11.24 MAP kinase
-
 eukaryota
2.7.11.24 MAPK
-
 eukaryota
2.7.11.24 p38
-
 eukaryota
2.7.12.2 MAPK kinase-1
-
 eukaryota

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.10.2 ATP dependent on eukaryota
2.7.11.11 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
2.7.11.19 ATP dependent on eukaryota
2.7.11.22 ATP dependent on eukaryota
2.7.11.24 ATP dependent on eukaryota
2.7.12.2 ATP dependent on eukaryota