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Literature summary for 2.7.11.31 extracted from
- Probing the enzyme kinetics, allosteric modulation and activation of alpha1- and alpha2-subunit-containing AMP-activated protein kinase (AMPK) heterotrimeric complexes by pharmacological and physiological activators (2016), Biochem. J., 473, 581-592.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| A769662 | A769662 selectively activates beta1-containing AMPK isoforms | Homo sapiens |  |
| AMP | the alpha2-subunit-containing enzyme complexes are more readily activated by AMP than alpha1-complexes | Homo sapiens | |
| additional information | all three nucleotides AMP, ADP and ATP can bind to sites 1 and 3 with similar affinities. Phosphorylation of Thr172/Thr174 of the alpha subunit activates the enzyme isozymes | Homo sapiens |
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | design and development of isoform-selective AMPK activators that are likely to be useful for the treatment of cardiovascular and metabolic diseases | Homo sapiens |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| recombinant coexpression of different His6-tagged subunit constructs in Escherichia coli strain BL21-CodonPlusTM (DE3)-RIPL, coexpression with biotin-ligase (BirA) | Homo sapiens |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | theMichaelis-Menten enzyme kinetics and allosteric modulation of six recombinant AMPK isoforms, alpha1beta1gamma1, alpha1beta2gamma1, alpha1beta2gamma3, alpha2beta1gamma1, alpha2beta2gamma,1 and alpha2beta2gamma3 using known activators, A769662 and AMP. The alpha1-containing complexes exhibit higher specific activities and lower Km values for peptide substrate biotin-GGHMRSAMSGLHLVKRR-NH2 (SAMS) compared with alpha2-complexes. Binding affinities of AMP, ADP and ATP using surface plasmon resonance techniques, all three nucleotides AMP, ADP and ATP can bind to sites 1 and 3 with similar affinities, allosteric regulation | Homo sapiens | |
| 0.02604 | - |
ATP | pH 7.5, 30°C, enzyme construct alpha1beta1gamma1 | Homo sapiens | |
| 0.02667 | - |
biotin-GGHMRSAMSGLHLVKRR-NH2 | pH 7.5, 30°C, enzyme construct alpha1beta1gamma1 | Homo sapiens | |
| 0.03135 | - |
ATP | pH 7.5, 30°C, enzyme construct alpha2beta1gamma1 | Homo sapiens | |
| 0.03207 | - |
biotin-GGHMRSAMSGLHLVKRR-NH2 | pH 7.5, 30°C, enzyme construct alpha1beta1gamma1 | Homo sapiens | |
| 0.03731 | - |
biotin-GGHMRSAMSGLHLVKRR-NH2 | pH 7.5, 30°C, enzyme construct alpha1beta1gamma1 | Homo sapiens | |
| 0.04506 | - |
ATP | pH 7.5, 30°C, enzyme construct alpha1beta2gamma1 | Homo sapiens | |
| 0.04797 | - |
ATP | pH 7.5, 30°C, enzyme construct alpha2beta2gamma1 | Homo sapiens | |
| 0.08003 | - |
biotin-GGHMRSAMSGLHLVKRR-NH2 | pH 7.5, 30°C, enzyme construct alpha1beta1gamma1 | Homo sapiens | |
| 0.1076 | - |
biotin-GGHMRSAMSGLHLVKRR-NH2 | pH 7.5, 30°C, enzyme construct alpha1beta1gamma1 | Homo sapiens | |
| 0.1214 | - |
biotin-GGHMRSAMSGLHLVKRR-NH2 | pH 7.5, 30°C, enzyme construct alpha1beta1gamma1 | Homo sapiens | |
| 0.3329 | - |
ATP | pH 7.5, 30°C, enzyme construct alpha1beta2gamma3 | Homo sapiens | |
| 0.4168 | - |
ATP | pH 7.5, 30°C, enzyme construct alpha2beta2gamma3 | Homo sapiens | |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Homo sapiens | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q13131 AND P54646 | AMPK subunit alpha-1a and alpha-2 | - |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| phosphoprotein | phosphorylation of Thr172/Thr174 of the alpha subunit activates the enzyme isozymes | Homo sapiens |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| different recombinant His6-tagged subunit constructs from Escherichia coli strain BL21-CodonPlusTM (DE3)-RIPL by nickel affinity chromatography and dialysis | Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + biotin-GGHMRSAMSGLHLVKRR-NH2 | i.e. SAMS peptide, a peptide derived from residues 73-85 of rat acetyl-CoA carboxylase in which Ser77 is mutated to Ala and the AMPK phosphorylation site is Ser79 | Homo sapiens | ADP + phosphorylated biotin-GGHMRSAMpSGLHLVKRR-NH2 | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| heterotrimer | AMPK exists as a heterotrimeric complex, composed of a catalytic subunit (alpha) and two regulatory subunits (beta and gamma), each present as multiple isoforms | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| AMP-activated protein kinase | - |
Homo sapiens |
| AMPK | - |
Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 30 | - |
assay at | Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.5 | - |
assay at | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Homo sapiens | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| additional information | alpha1-subunit containing AMPK isoforms possess higher basal activity and are less sensitive to desphosphorylation by phosphatases compared with alpha2-subunit containing heterotrimers. The alpha2-subunit-containing complexes are more readily activated by AMP than alpha1-complexes. Enzymatic activity, phosphatase sensitivity and kinetics of alpha1- and alpha2-containing AMPK isoforms, differential effect of activators, overview | Homo sapiens |
| physiological function | AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that serves as a pleotropic regulator of whole body energy homoeostasis. The enzyme is allosterically regulated, kinetic analysis, overview. Binding of activator AMP to the gamma-subunit allows a small regulatory segment of the alpha-subunit (alpha2 residues 365-371) called the alpha-hook or alpha-RIM2 to directly interact with bound AMP and create an allosteric conformational change at the catalytic active site. As a consequence, the phosphorylated alpha-Thr172/174 can be protected from dephosphorylation by phosphatases and sustain its kinase activity for an extended period | Homo sapiens |
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