Any feedback?
Literature summary for 2.7.11.31 extracted from
- Structure and function of AMP-activated protein kinase (2009), Acta Physiol. (Oxf.), 196, 3-14.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| additional information | ADP does not directly control AMPK activity but can do so indirectly through the adenylate kinase equilibrium with AMP and ATP | Mus musculus | |
| additional information | AMP does not activate the SNF1 complex | Saccharomyces cerevisiae |
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | AMPK is regarded as one of the most promising targets for new drugs to treat the growing incidence of metabolic diseases such as obesity and type 2 diabetes and cardiovascular disease | Mus musculus |
| drug development | AMPK is regarded as one of the most promising targets for new drugs to treat the growing incidence of metabolic diseases such as obesity and type 2 diabetes and cardiovascular disease | Homo sapiens |
| drug development | AMPK is regarded as one of the most promising targets for new drugs to treat the growing incidence of metabolic diseases such as obesity and type 2 diabetes and cardiovascular disease | Rattus norvegicus |
| drug development | AMPK is regarded as one of the most promising targets for new drugs to treat the growing incidence of metabolic diseases such as obesity and type 2 diabetes and cardiovascular disease | Sus scrofa |
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| crystal structure of AMPK beta1 subunit-carbohydrate-binding module in complex with the cyclic sugar beta-cyclodextrin shows that the domain consists of a beta-hairpin loop extending from a beta-sandwich containing two anti-parallel beta-sheets. The sugar ring is held in position by the beta-hairpin loop, which protrudes the ring with Leu-146 at its centre. Within the sugarbinding pocket an extensive network of hydrophobic stacking interactions, mediated by Trp100 and Trp133, and carbohydrate-protein hydrogen bonds are formed with five of the seven glucose units. Although Leu-146 is prominent in the beta7-beta8 hairpin and interacts extensively with beta-cyclodextrin, it is not essential for glycogen binding | Rattus norvegicus |
| crystal structure of the inactive, apo-form of AMPK alpha2 subunit N-terminal kinase catalytic domain (KCD, residues 10-278 inclusive), shows that it adopts a canonical bilobal structure with the active site forming a cleft between the two lobes. The small N-terminal lobe (residues 1-97) is composed of a five-stranded beta-sheet (beta1-beta5), with an alpha-helix (termed the C-helix) positioned between strands beta3 and beta4 and lying to one side of the beta sheet. Glu-64 within the C-helix is important for aligning the phosphates of ATP in the correct orientation for catalysis. A Gly-X-Gly-X-X-Gly P-loop motif connecting strands beta1 and beta2 is evident in the structure. This interacts with the beta phosphate group of ATP when the active site is occupied. The larger C-terminal lobe is predominantly (63%) alpha-helical (alphaD-alphaI) and contains determinants and structural features that dictate protein substrate binding. The two lobes are connected via a short, flexible hinge region that allows rotation of the two lobes relative to each other | Homo sapiens |
| crystal structures for full-length Snf4 | Saccharomyces cerevisiae |
| crystal structures for full-length Snf4. In the subunit crystal structure ADP can be co-crystallized and occupies site 2, the unoccupied site present in mammalian gamma1 | Schizosaccharomyces pombe |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| additional information | contraction in skeletal muscle in adenylate kinase null mice reduces AMPK activation due to lack of conversion of ADP to AMP | Mus musculus |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytoplasm | Gal83 directs Snf1 to the cytoplasm | Saccharomyces cerevisiae | 5737 | - |
| nucleus | Sip1 directs Snf1 to the nucleus | Saccharomyces cerevisiae | 5634 | - |
| vacuole | Sip2 directs Snf1 to the vacuole | Saccharomyces cerevisiae | 5773 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | Asp-157 within the DFG motif is required for binding the Mg2+ ion that co-ordinates beta and gamma phosphates of Mg2+-ATP in the active site | Homo sapiens |  |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Mus musculus | - |
- |
- |
| Rattus norvegicus | - |
- |
- |
| Saccharomyces cerevisiae | - |
- |
- |
| Schizosaccharomyces pombe | - |
- |
- |
| Sus scrofa | - |
- |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| liver | - |
Mus musculus | - |
| skeletal muscle | - |
Mus musculus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | Snf4 subunit contains cystathionine-beta-synthase (CBS) sequence repeats. CBS4 can be occupied either by AMP, ZMP or ATP, and CBS2 by ADP | Schizosaccharomyces pombe | ? | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| heterotrimer | - |
Saccharomyces cerevisiae |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| AMP-activated protein kinase | - |
Mus musculus |
| AMP-activated protein kinase | - |
Homo sapiens |
| AMP-activated protein kinase | - |
Rattus norvegicus |
| AMP-activated protein kinase | - |
Sus scrofa |
| AMPK | - |
Mus musculus |
| AMPK | - |
Homo sapiens |
| AMPK | - |
Rattus norvegicus |
| AMPK | - |
Sus scrofa |
| Snf1 | homologue of mammalian AMPK catalytic alpha subunit | Saccharomyces cerevisiae |
| Snf1 | homologue of mammalian AMPK catalytic alpha subunit | Schizosaccharomyces pombe |
| SNF4 | homologue of mammalian AMPK catalytic gamma1 subunit | Saccharomyces cerevisiae |
| SNF4 | homologue of mammalian AMPK catalytic gamma1 subunit | Schizosaccharomyces pombe |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Homo sapiens | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | in the liver from beta1 knockout mice the gamma1 subunit is present but alpha1 and alpha2 are degraded | Mus musculus |
| malfunction | mutations in the gamma2 and gamma3 subunits result in glycogen storage disease | Sus scrofa |
| malfunction | mutations in the gamma2 and gamma3 subunits result in glycogen storage disease. Ten point mutations in gamma2 are associated with a glycogen storage cardiomyopathy and ventricular pre-excitation | Homo sapiens |
| metabolism | is a key regulator of cellular and whole-body energy homeostasis that co-ordinates metabolic pathways in order to balance nutrient supply with energy demand | Mus musculus |
| metabolism | is a key regulator of cellular and whole-body energy homeostasis that co-ordinates metabolic pathways in order to balance nutrient supply with energy demand | Homo sapiens |
| metabolism | is a key regulator of cellular and whole-body energy homeostasis that co-ordinates metabolic pathways in order to balance nutrient supply with energy demand | Rattus norvegicus |
| metabolism | is a key regulator of cellular and whole-body energy homeostasis that co-ordinates metabolic pathways in order to balance nutrient supply with energy demand | Sus scrofa |
| metabolism | SNF1 protein kinase cascade, sharing functional similarities with mammalian AMPK, which plays an important role in adapting the unicellular eukaryote to glucose starvation | Saccharomyces cerevisiae |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
