Activating Compound | Comment | Organism | Structure |
---|---|---|---|
adiponectin | activates the ceramidase activity of adiponectin receptor ADIPOR2 about 20fold. Adiponectin is a hormone, secreted mainly from adipocytes, that stimulates glucose utilization and fatty-acid oxidation | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
purified recombinant ADIPOR2 complexed with a free fatty acid molecule, X-ray diffraction structure determination and analysis | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | Michaelis-Menten kinetic analysis | Homo sapiens | |
0.0156 | - |
C18-ceramide | pH and temperature not specified in the publication | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
membrane | ADIPOR2 contains 7 transmembrane segments | Homo sapiens | 16020 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Zn2+ | required for catalysis, enzyme-bound | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ceramide + H2O | Homo sapiens | - |
fatty acid + sphingosine | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q86V24 | - |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
C18-ceramide + H2O | preferred substrate, fluorescent C18 ceramide in detergent micelles | Homo sapiens | stearate + sphingosine | - |
? | |
C24-ceramide + H2O | - |
Homo sapiens | lignocerate + sphingosine | - |
? | |
C6-ceramide + H2O | - |
Homo sapiens | hexanoate + sphingosine | - |
? | |
ceramide + H2O | - |
Homo sapiens | fatty acid + sphingosine | - |
? | |
additional information | ADIPOR2 may have a preference for C18 ceramide substrate, but can also hydrolyse shorter (C6 ceramide) and longer (C24 ceramide) substrates, but to a lesser extent. Low overall ceramidase catalytic activity of ADIPOR2. Substrate binding structure, overview. The substrate amide carbonyl contacts the R278TM5 and Y328TM6 side chains, which are typical carbonyl-polarizing and oxyanion-stabilizing residues in zinc-dependent hydrolases | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | the crystal structures of the two receptor subtypes, ADIPOR1 and ADIPOR2, show a similar overall seven-transmembranedomain architecture with large unoccupied cavities and a zinc binding site within the seven transmembrane domain | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
adiponectin receptor | - |
Homo sapiens |
ADIPOR2 | - |
Homo sapiens |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.00049 | - |
C18-ceramide | pH and temperature not specified in the publication | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
evolution | ADIPORs display distant homology with alkaline ceramidases, comparison of structures of ADIPOR1 and ADIPOR2 | Homo sapiens |
metabolism | adiponectin receptors (ADIPORs) are integral membrane proteins that control glucose and lipid metabolism by mediating, at least in part, a cellular ceramidase activity that catalyses the hydrolysis of ceramide to produce sphingosine and a free fatty acid. ADIPOR2 possesses intrinsic basal ceramidase activity that is enhanced by adiponectin | Homo sapiens |
additional information | possible mechanism for the hydrolytic activity of ADIPOR2 using computational approaches. In molecular dynamics simulations, the side chains of residues coordinating the zinc rearrange quickly to promote the nucleophilic attack of a zinc-bound hydroxide ion onto the ceramide amide carbonyl. Enzyme structure analysis, overbiew. An uninterrupted cavity goes through the entire receptor from the domain exposed to the upper lipid bilayer to the domain exposed to the cytoplasm. A tunnel enters the top half of the receptor between TM5 and TM6 and links the upper lipid bilayer to the FFA binding pocket. Some electron density is present in this domain indicating that this large opening might play a key role in modulating the entrance or exit of molecules to or from the receptor. On the intracellular side of ADIPOR2, the cavity splits into two tunnels immediately below the zinc binding domain, one of which is largely exposed to the cytoplasm | Homo sapiens |
kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.031 | - |
C18-ceramide | pH and temperature not specified in the publication | Homo sapiens |