FAAH1 Antibody (Rabbit mAb) [H15C21] Datasheet

Biological Description

Specificity	FAAH1 Antibody (Rabbit mAb) [H15C21] detects endogenous levels of total FAAH1 protein.
Background	FAAH belongs to the amidase signature enzyme family and functions as the principal catabolic regulator of neuromodulatory fatty acid amides, most notably the endocannabinoid anandamide, hydrolyzing it into arachidonic acid and ethanolamine to terminate cannabinoid receptor signaling. The enzyme carries a predicted N-terminal transmembrane domain, a glycine- and serine-rich amidase signature sequence, a polyproline region predicted to interact with Homer and SH3-domain-containing proteins, and a monotopic membrane-binding domain, and it assembles as a homodimer in its membrane-associated form rather than functioning as a soluble monomeric enzyme. Unlike the great majority of mammalian serine hydrolases, which rely on a canonical Ser-His-Asp catalytic triad, FAAH employs an unusual serine-serine-lysine triad, Ser241-Ser217-Lys142, in which Lys142 begins in a deprotonated state and abstracts a proton from Ser217, which in turn abstracts a proton from the Ser241 nucleophile, coupling nucleophilic attack on the substrate carbonyl to simultaneous proton donation from Ser217 to the leaving nitrogen atom of the amide substrate. Site-directed mutagenesis of each triad residue shows that they contribute distinct, non-redundant roles to catalysis: Lys142 functions both as the base activating the Ser241 nucleophile and as an acid protonating the substrate leaving group, a dual function that explains FAAH's unusual ability to hydrolyze amide and ester substrates at comparable rates, while mutation of the bridging Ser217 residue impairs overall catalytic activity without altering this amide-to-ester hydrolysis ratio, indicating that Ser217's contribution is mechanistically separable from Lys142's dual acid-base function. Substrate access to this buried catalytic triad proceeds through a membrane-access channel connecting the membrane surface to the enzyme core, where charged residues favor entry of the polar head groups of fatty acid amides, while an adjacent acyl-chain-binding channel accommodates the hydrophobic tail of the substrate, and a gating pair of residues positioned at the boundary between these two channels controls lipid selection, restricting which bioactive lipids can access the catalytic site. Once hydrolysis is complete, a separate cytosolic port allows the reaction products to exit the enzyme. FAAH terminates anandamide signaling at cannabinoid receptors; its distribution across brain, liver, kidney, and testis positions it as a direct regulator of endocannabinoid tone at the tissue level, and FAAH is pursued as a therapeutic target for pain, anxiety, hypertension, and inflammatory conditions.

Specificity

FAAH1 Antibody (Rabbit mAb) [H15C21] detects endogenous levels of total FAAH1 protein.

Background

FAAH belongs to the amidase signature enzyme family and functions as the principal catabolic regulator of neuromodulatory fatty acid amides, most notably the endocannabinoid anandamide, hydrolyzing it into arachidonic acid and ethanolamine to terminate cannabinoid receptor signaling. The enzyme carries a predicted N-terminal transmembrane domain, a glycine- and serine-rich amidase signature sequence, a polyproline region predicted to interact with Homer and SH3-domain-containing proteins, and a monotopic membrane-binding domain, and it assembles as a homodimer in its membrane-associated form rather than functioning as a soluble monomeric enzyme. Unlike the great majority of mammalian serine hydrolases, which rely on a canonical Ser-His-Asp catalytic triad, FAAH employs an unusual serine-serine-lysine triad, Ser241-Ser217-Lys142, in which Lys142 begins in a deprotonated state and abstracts a proton from Ser217, which in turn abstracts a proton from the Ser241 nucleophile, coupling nucleophilic attack on the substrate carbonyl to simultaneous proton donation from Ser217 to the leaving nitrogen atom of the amide substrate. Site-directed mutagenesis of each triad residue shows that they contribute distinct, non-redundant roles to catalysis: Lys142 functions both as the base activating the Ser241 nucleophile and as an acid protonating the substrate leaving group, a dual function that explains FAAH's unusual ability to hydrolyze amide and ester substrates at comparable rates, while mutation of the bridging Ser217 residue impairs overall catalytic activity without altering this amide-to-ester hydrolysis ratio, indicating that Ser217's contribution is mechanistically separable from Lys142's dual acid-base function. Substrate access to this buried catalytic triad proceeds through a membrane-access channel connecting the membrane surface to the enzyme core, where charged residues favor entry of the polar head groups of fatty acid amides, while an adjacent acyl-chain-binding channel accommodates the hydrophobic tail of the substrate, and a gating pair of residues positioned at the boundary between these two channels controls lipid selection, restricting which bioactive lipids can access the catalytic site. Once hydrolysis is complete, a separate cytosolic port allows the reaction products to exit the enzyme. FAAH terminates anandamide signaling at cannabinoid receptors; its distribution across brain, liver, kidney, and testis positions it as a direct regulator of endocannabinoid tone at the tissue level, and FAAH is pursued as a therapeutic target for pain, anxiety, hypertension, and inflammatory conditions.

Usage Information

Application

WB, IHC

Dilution

WB	IHC
1:1000	1:250 - 1:500

Reactivity

Human

Source

Rabbit Monoclonal Antibody

MW

63 kDa

Storage Buffer

PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage
(from the date of receipt)

-20°C (avoid freeze-thaw cycles), 2 years

References

https://pubmed.ncbi.nlm.nih.gov/12734197/
https://pubmed.ncbi.nlm.nih.gov/20544003/

FAAH1 Antibody (Rabbit mAb) [H15C21]

Biological Description

Usage Information

References

Application Data