Cloned (Comment) | Organism |
---|---|
expression of mutant L192F/F194Y/A377T/S435N/I491V/V495M in Escherichia coli strain BL21 | Rattus norvegicus |
Crystallization (Comment) | Organism |
---|---|
recombinant fatty acid amide hydrolase mutant L192F/F194Y/A377T/S435N/I491V/V495M bound to carbamate inhibitor URB597 or inhibitor PF-3845, 25-30 mg/ml protein in 10 mM HEPES, pH 7.0, 500 mM NaCl, 2 mM dithiothreitol, and 0.08% n-undecyl-beta-D-maltoside or 0.1% n-decyl-beta-D-maltoside for inhibitor URB597-enzyme or PF-3845-enzyme conjugate, respectively, supplementation of the FAAHURB597 proteinsample with 1.6% benzyldimethyl(2-dodecyloxyethyl)-ammonium chloride and mixed at a 1:1 proportion with a crystallization buffer containing 30% PEG 400, 100 mM TrisHCl pH 7.5, and 100 mM MgCl2, supplementation of the FAAHPF-3845 protein sample with 1.6% benzyl-dimethyl-dodecyl ammonium bromide and mixed at a 1:1 ratio with a crystallization buffer containing 30% PEG 400, 100 mM 2-(N-morpholino)ethanesulfonate/NaOH, pH 5.5, and 400 mM LiCl, sitting drop vapor diffusion at 14°C, X-ray diffraction structure determination and analysis at 2.3 A resolution | Rattus norvegicus |
Protein Variants | Comment | Organism |
---|---|---|
L192F/F194Y/A377T/S435N/I491V/V495M | generation of a humanized version of the rat FAAH by replacment of six amino acids in the active site of the rat FAAH protein in order to recreate the binding profile of the human enzyme | Rattus norvegicus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
PF-3845 | crystal structure analysis of enzyme-inhibitor complex. The inhibitor interacts with the catalytic triad and oxyanion hole residues | Rattus norvegicus | |
URB524 | - |
Rattus norvegicus | |
URB597 | a carbamate inhibitor that displays excellent selectivity for FAAH in the nervous system, although the inhibitor does inactivate additional peripheral hydrolases, enzyme-inhibitor binding structure, overview. The inhibitor interacts with the catalytic triad and oxyanion hole residues | Rattus norvegicus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
membrane | - |
Rattus norvegicus | 16020 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
anandamide + H2O | Rattus norvegicus | i.e. arachidonoyl ethanolamide | arachidonic acid + ethanolamine | - |
? | |
oleamide + H2O | Rattus norvegicus | i.e. cis-9-octadecenamide | oleic acid + NH3 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Rattus norvegicus | P97612 | recombinant mutant L192F/F194Y/A377T/S435N/I491V/V495M, a humanized version of the rat FAAH | - |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
anandamide + H2O = arachidonic acid + ethanolamine | structure-function relationship and catalytic mechanism, overview | Rattus norvegicus | |
oleamide + H2O = oleic acid + NH3 | structure-function relationship and catalytic mechanism, overview | Rattus norvegicus |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
anandamide + H2O | i.e. arachidonoyl ethanolamide | Rattus norvegicus | arachidonic acid + ethanolamine | - |
? | |
oleamide + H2O | i.e. cis-9-octadecenamide | Rattus norvegicus | oleic acid + NH3 | - |
? |
Synonyms | Comment | Organism |
---|---|---|
FAAH | - |
Rattus norvegicus |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0000046 | - |
pH and temperature not specified in the publication | Rattus norvegicus | URB597 | |
0.000063 | - |
pH and temperature not specified in the publication | Rattus norvegicus | URB524 |
General Information | Comment | Organism |
---|---|---|
evolution | FAAH is a member of the amidase signature family found in bacteria, archaea and eukaryotes | Rattus norvegicus |
physiological function | fatty acid amide hydrolase degrades lipid signaling molecules such as the endogenous cannabinoids anandamide, i.e. N-arachidonyl ethanolamine, and the sleep-inducing substance oleamide, i.e. cis-9-octadecenamide | Rattus norvegicus |