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 | 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 (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 | 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 | 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 | 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 | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Mus musculus | - |
- |
- |
Rattus norvegicus | - |
- |
- |
Saccharomyces cerevisiae | - |
- |
- |
Schizosaccharomyces pombe | - |
- |
- |
Sus scrofa | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
liver | - |
Mus musculus | - |
skeletal muscle | - |
Mus musculus | - |
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 | Comment | Organism |
---|---|---|
heterotrimer | - |
Saccharomyces cerevisiae |
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 | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Homo sapiens |
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 |