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Literature summary for 2.7.11.17 extracted from

  • Kukimoto-Niino, M.; Yoshikawa, S.; Takagi, T.; Ohsawa, N.; Tomabechi, Y.; Terada, T.; Shirouzu, M.; Suzuki, A.; Lee, S.; Yamauchi, T.; Okada-Iwabu, M.; Iwabu, M.; Kadowaki, T.; Minokoshi, Y.; Yokoyama, S.
    Crystal structure of the Ca2+/calmodulin-dependent protein kinase kinase in complex with the inhibitor STO-609 (2011), J. Biol. Chem., 286, 22570-22579.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expression in Escherichia coli Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
hanging drop vapor diffusion method at 20°C, crystal structure of the catalytic kinase domain of the human CaMKKbeta isoform complexed with its selective inhibitor 7H-benzimidazo(2,1-a)benz(de)isoquinoline-7-one-3-carboxylate (i.e. STO-609). The crystal belongs to the primitive orthorhombic space group P2(1)2(1)2(1) with unit cell constants of a = 69.4 A, b = 77.2 A, c = 84.3 A Homo sapiens

Protein Variants

Protein Variants Comment Organism
P274E the P274E mutation significantly reduces the inhibitory effect of 7H-benzimidazo(2,1-a)benz(de)isoquinoline-7-one-3-carboxylate (i.e. STO-609) on the isoenzyme CaMKKbeta Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
7H-benzimidazo(2,1-a)benz(de)isoquinoline-7-one-3-carboxylate i.e. STO-609. The CaMKKbeta residue Pro274, which replaces the conserved acidic residue of other protein kinases, is an important determinant for the selective inhibition by STO-609. ATP-competitive inhibition mechanism Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + Ca2+/calmodulin-dependent protein kinase I Homo sapiens the enzyme is a member of the CaMK cascade that mediates the response to intracellular Ca2+ elevation. Ca2+/calmodulin-dependent protein kinase kinase phosphorylates and activates Ca2+/calmodulin-dependent protein kinase I and Ca2+/calmodulin-dependent protein kinase IV, which directly activate transcription factors ADP + phosphorylated Ca2+/calmodulin-dependent protein kinase I
-
?
ATP + Ca2+/calmodulin-dependent protein kinase IV Homo sapiens the enzyme is a member of the CaMK cascade that mediates the response to intracellular Ca2+ elevation. Ca2+/calmodulin-dependent protein kinase kinase phosphorylates and activates Ca2+/calmodulin-dependent protein kinase I and Ca2+/calmodulin-dependent protein kinase IV, which directly activate transcription factors ADP + phosphorylated Ca2+/calmodulin-dependent protein kinase IV
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q96RR4
-
-

Purification (Commentary)

Purification (Comment) Organism
-
Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + Ca2+/calmodulin-dependent protein kinase I
-
Homo sapiens ADP + phosphorylated Ca2+/calmodulin-dependent protein kinase I
-
?
ATP + Ca2+/calmodulin-dependent protein kinase I the enzyme is a member of the CaMK cascade that mediates the response to intracellular Ca2+ elevation. Ca2+/calmodulin-dependent protein kinase kinase phosphorylates and activates Ca2+/calmodulin-dependent protein kinase I and Ca2+/calmodulin-dependent protein kinase IV, which directly activate transcription factors Homo sapiens ADP + phosphorylated Ca2+/calmodulin-dependent protein kinase I
-
?
ATP + Ca2+/calmodulin-dependent protein kinase IV
-
Homo sapiens ADP + phosphorylated Ca2+/calmodulin-dependent protein kinase IV
-
?
ATP + Ca2+/calmodulin-dependent protein kinase IV the enzyme is a member of the CaMK cascade that mediates the response to intracellular Ca2+ elevation. Ca2+/calmodulin-dependent protein kinase kinase phosphorylates and activates Ca2+/calmodulin-dependent protein kinase I and Ca2+/calmodulin-dependent protein kinase IV, which directly activate transcription factors Homo sapiens ADP + phosphorylated Ca2+/calmodulin-dependent protein kinase IV
-
?

Synonyms

Synonyms Comment Organism
Ca2+/calmodulin-dependent protein kinase kinase
-
Homo sapiens
CaMK
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Homo sapiens
CaMKK
-
Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.02
-
30°C, pH 7.5, mutant enzyme P274E Homo sapiens 7H-benzimidazo(2,1-a)benz(de)isoquinoline-7-one-3-carboxylate
0.5
-
30°C, pH 7.5, wild-type enzyme Homo sapiens 7H-benzimidazo(2,1-a)benz(de)isoquinoline-7-one-3-carboxylate

General Information

General Information Comment Organism
physiological function the enzyme is a member of the CaMK cascade that mediates the response to intracellular Ca2+ elevation Homo sapiens