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Information on EC 3.5.1.60 - N-(long-chain-acyl)ethanolamine deacylase and Organism(s) Homo sapiens
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3.5.1.60 N-(long-chain-acyl)ethanolamine deacylaseIUBMB Comments
This lysosomal enzyme acts best on palmitoyl ethanolamide, with lower activity on other N-(long-chain-acyl)ethanolamines. It is only active at acidic pH. Unlike EC 3.5.1.99, fatty acid amide hydrolase, it does not act on primary amides such as oleamide, and has only a marginal activity with anandamide. The enzyme is translated as an inactive proenzyme, followed by autocatalytic cleavage into two subunits that reassociate to form an active heterodimeric complex.
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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
hnaaa, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
amidase, acylethanolamine
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-
-
-
N-acylethanolamine acid amidase
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N-acylethanolamine amidohydrolase
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-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of linear amides
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SYSTEMATIC NAME
IUBMB Comments
N-(long-chain-acyl)ethanolamine amidohydrolase
This lysosomal enzyme acts best on palmitoyl ethanolamide, with lower activity on other N-(long-chain-acyl)ethanolamines. It is only active at acidic pH. Unlike EC 3.5.1.99, fatty acid amide hydrolase, it does not act on primary amides such as oleamide, and has only a marginal activity with anandamide. The enzyme is translated as an inactive proenzyme, followed by autocatalytic cleavage into two subunits that reassociate to form an active heterodimeric complex.
CAS REGISTRY NUMBER
COMMENTARY
99283-61-1
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
N-alpha-linolenoylethanolamide + H2O
alpha-linoleate + ethanolamine
-
-
-
?
N-eicosapentaenoylethanolamide + H2O
eicosapentanoate + ethanolamine
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-
-
?
N-palmitoylethanolamide + H2O
palmitate + ethanolamine
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-
-
?
additional information
?
-
N-acylethanolamine acid amidase is a cysteine amidase that hydrolyzes saturated or monounsaturated fatty acid ethanolamides, such as palmitoylethanolamide and oleoylethanolamide
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-
?
N-(4-methylcoumarin)palmitamide + H2O
palmitic acid + 7-amino-4-methylcoumarin
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-
-
?
N-(4-methylcoumarin)palmitamide + H2O
palmitic acid + 7-amino-4-methylcoumarin
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-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
N-alpha-linolenoylethanolamide + H2O
alpha-linoleate + ethanolamine
-
-
-
?
N-eicosapentaenoylethanolamide + H2O
eicosapentanoate + ethanolamine
-
-
-
?
N-palmitoylethanolamide + H2O
palmitate + ethanolamine
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-
-
?
additional information
?
-
N-acylethanolamine acid amidase is a cysteine amidase that hydrolyzes saturated or monounsaturated fatty acid ethanolamides, such as palmitoylethanolamide and oleoylethanolamide
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-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
([1,1'-biphenyl]-4-yl)methyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate
inhibition through a rapid and noncompetitive mechanism, partially reversible inhibition. The compound reacts with the catalytically active N-terminal Cys126 of human enzyme to form a thioester bond
3,5-dichloro-4-nitropyridine
AM11095, synthetis of the specific brain permeable NAAA inhibitor, a slowly reversible NAAA inhibitor
3-[6-(3-chlorophenyl)hexanoyl]-1,3-oxazolidin-2-one
i.e. F215, the NAAA inhibitor F215 is a therapeutic agent for osteoarthritis
4-cyclohexylbutyl [(3S)-2-oxoazetidin-3-yl]carbamate
a serine-derived beta-lactam CC-ABP, competitive
5-((biphenyl-4-yl)methyl)-N,N-dimethyl-2H-tetrazole-2-carboxamide
inhibits the enzyme in a covalent and irreversible manner
5-(4-(4-(5,5-difluoro-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-10-yl)butyl)-1H-1,2,3-triazol-1-yl)pentyl ((2S,3S)-2-methyl-1-(4-(methylsulfonyl)phenoxy)-4-oxoazetidin-3-yl)carbamate
a N-O-substituted beta-lactam BODIPY-ABP, almost complete inhibition of enzyme NAAA
5-(norbornan-2-ylmethoxy)pentyl N-[(2S,3S)-2-methyl-1-(4-methylsulfonylphenoxy)-4-oxo-azetidin-3-yl]carbamate
a norbornene-derived beta-lactam
5-azidopentyl N-[(2S,3S)-2-methyl-1-(4-methylsulfonylphenoxy)-4-oxo-azetidin-3-yl]carbamate
an azide-beta-lactam
N-benzyloxycarbonyl-L-serine beta-lactone
inhibits the enzyme in a covalent and irreversible manner
palmitic acid retro-amides N-pentadecylbenzamide
a potent and selective inhibitor
tert-butyl ((2S,3S)-2-methyl-1-(4-(methylsulfonyl)phenoxy)-4-oxoazetidin-3-yl)carbamate
-
undec-10-ynyl-N-[(3S)-2-oxoazetidin-3-yl]carbamate
ARN14686, design and validation of this derivative of ARN726 as activity-based protein profiling (ABPP) probe for the in vivo detection of NAAA
[2-(ethylsulfonyl)phenyl][(2S)-4-(6-fluoro-1,3-benzothiazol-2-yl)-2-methylpiperazin-1-yl]methanone
ARN19702, a noncovalent benzothiazole-piperazine derivative
1-isothiocyanatopentadecane
a potent, competitive, selective, and reversible inhibitor
4-cyclohexylbutyl-N-[(S)-2-oxoazetidin-3-yl]carbamate
it blocks enzyme NAAA by covalently binding to the enzyme's catalytic cysteine and displays pronounced antiinflammatory properties in human macrophages
4-cyclohexylbutyl-N-[(S)-2-oxoazetidin-3-yl]carbamate
ARN726, the enzyme inhibitor exerts systemic anti-inflammatory effects in mouse models of lung inflammation
4-cyclohexylbutyl-N-[(S)-2-oxoazetidin-3-yl]carbamate
ARN726, a beta-lactam that irreversibly reacts with Cys126
5-phenylpentyl-N-[(2S,3R)-2-methyl-4-oxo-oxetan-3-yl]carbamate
ARN077, the enzyme inhibitor is active in vivo by topical administration in rodent models of hyperalgesia and allodynia
additional information
synthesis and evaluation of a series of N-(2-oxoazetidin-3-yl)amides as a novel class of enzyme inhibitors with good potency and improved physicochemical properties, suitable for systemic administration. No inhibition by 3-phenyl-N-[(S)-2-oxoazetidin-3-yl]propanamide, N-[(3S)-2-oxoazetidin-3-yl][1,1'-biphenyl]-4-carboxamide, N-(2-oxocyclobutyl)nonanamide, N-(azetidin-3-yl)nonanamide, 3-amino-N-nonanoyl-L-alanine, N-[(3S)-2-oxopyrrolidin-3-yl]nonanamide, N-[(S)-1-methyl-2-oxo-azetidin-3-yl]nonanamide, N-methyl-N-[(S)-2-oxoazetidin-3-yl]nonanamide, and (S)-3-(nonylamino)azetidin-2-one
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additional information
selective alkylation of the enzyme's cysteine residues results in almost complete loss of activity
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additional information
mechanism of inactivation of human enzyme N-acylethanolamine-hydrolyzing acid amidase with selected inhibitors identified in a fluorescent based assay developed for characterization of both reversible and irreversible inhibitors, kinetic analysis using MALDI-TOF mass spectroscopy, molecular modeling, overview
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additional information
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mechanism of inactivation of human enzyme N-acylethanolamine-hydrolyzing acid amidase with selected inhibitors identified in a fluorescent based assay developed for characterization of both reversible and irreversible inhibitors, kinetic analysis using MALDI-TOF mass spectroscopy, molecular modeling, overview
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additional information
inhibitor desing and synthesis of a class of beta-lactam derivatives that are potent, selective, and systemically active inhibitors of intracellular NAAA activity, reaction mechanisms via acylation or alkylation of the enzyme, overview
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additional information
inhibitor binding analysis using purified and activated human enzyme hNAAA coupled to an azide-PEG3-biotin conjugate to its terminal alkyne using click chemistry, and visualization of protein bands using streptavidin-horseradish peroxidase (HRP)
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additional information
identification of N-acylethanolamine-hydrolyzing acid amidase inhibitors able to reduce cell proliferation and migration and cause cell death on different bladder cancer cell lines. Inhibitor design of NAAA palmitic acid-retroamide inhibitors, synthesis, and characterization. Fluorescence high-throughput screening method set-up on human recombinant NAAA, using non-fluorescent but fluorogenic N-(4-methylcoumarin)palmitamide (PAMCA), that also allows to characterize the mechanism of inhibition. Reversibility of the inhibition. The NAAA inhibitors affect bladder cancer cells viability, they can be effective in inducing tumor cell death. But the inhibitors are differently effective of the different cell lines, overview
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additional information
development of two unprecedented NAAA-reactive activity-based probes as research tools for application in the discovery of inhibitors and for the in-depth characterization of NAAA in its cellular environment. Assay with lysosome-enriched extracts from hNAAA-overexpressing HEK-293 cells
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additional information
NAAA inhibitors block the substrate-binding site
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
the enzyme is proteolytically activated by an autocatalytic step under acidic conditions where the polypeptide is cleaved into two chains
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.021
N-palmitoylethanolamine
recombinant enzyme, pH not specified in the publication, 37°C
additional information
additional information
Michaelis-Menten kinetics
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0.0062
N-(4-methylcoumarin)palmitamide
recombinant enzyme, pH not specified in the publication, 37°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000013
5-((biphenyl-4-yl)methyl)-N,N-dimethyl-2H-tetrazole-2-carboxamide
recombinant enzyme, pH not specified in the publication, 37°C
0.0013
N-benzyloxycarbonyl-L-serine beta-lactone
recombinant enzyme, pH not specified in the publication, 37°C
additional information
additional information
inhibition kinetic analysis
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.02
(2R)-2-hydroxy-N-pentadecyl-2-phenylacetamide
Homo sapiens
pH and temperature not specified in the publication
0.000007
([1,1'-biphenyl]-4-yl)methyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate
Homo sapiens
pH and temperature not specified in the publication
0.011
2-hydroxy-N-pentadecylbenzamide
Homo sapiens
pH and temperature not specified in the publication
0.00002
3,5-dichloro-4-nitropyridine
Homo sapiens
pH and temperature not specified in the publication
0.00035
5-(4-(4-(5,5-difluoro-1,3,7,9-tetramethyl-5H-4l4,5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-10-yl)butyl)-1H-1,2,3-triazol-1-yl)pentyl ((2S,3S)-2-methyl-1-(4-(methylsulfonyl)phenoxy)-4-oxoazetidin-3-yl)carbamate
Homo sapiens
pH 7.4, 37°C
0.00006
5-(norbornan-2-ylmethoxy)pentyl N-[(2S,3S)-2-methyl-1-(4-methylsulfonylphenoxy)-4-oxo-azetidin-3-yl]carbamate
Homo sapiens
pH 7.4, 37°C
0.05
5-phenylpentyl N-[(2S,3R)-2-methyl-4-oxo-oxetan-3-yl]-carbamate
Homo sapiens
pH 4.5, 37°C
0.000007
5-phenylpentyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate
Homo sapiens
pH and temperature not specified in the publication
0.000007
5-phenylpentyl-N-[(2S,3R)-2-methyl-4-oxo-oxetan-3-yl]carbamate
Homo sapiens
pH and temperature not specified in the publication
0.01
cyclopentyl hexadecanoate
Homo sapiens
pH and temperature not specified in the publication
0.045
N-pentadecylbenzamide
Homo sapiens
pH and temperature not specified in the publication
0.034
N-pentadecylbutanamide
Homo sapiens
pH and temperature not specified in the publication
0.1
N-pentadecylnaphthalene-2-carboxamide
Homo sapiens
above, pH and temperature not specified in the publication
0.000006
undec-10-ynyl-N-[(3S)-2-oxoazetidin-3-yl]carbamate
Homo sapiens
pH and temperature not specified in the publication
0.00023
[2-(ethylsulfonyl)phenyl][(2S)-4-(6-fluoro-1,3-benzothiazol-2-yl)-2-methylpiperazin-1-yl]methanone
Homo sapiens
pH 4.5, 37°C, recombinant enzyme
0.078
(2S)-2-hydroxy-N-pentadecyl-2-phenylacetamide
Homo sapiens
pH and temperature not specified in the publication
0.00035
1-isothiocyanatopentadecane
Homo sapiens
recombinant enzyme with substrate N-(4-methyl coumarin)palmitamide, pH not specified in the publication, 37°C
0.00035 - 0.0006
1-isothiocyanatopentadecane
Homo sapiens
pH and temperature not specified in the publication
0.0006
1-isothiocyanatopentadecane
Homo sapiens
recombinant enzyme with substrate N-palmitoylethanolamine, pH not specified in the publication, 37°C
0.038
2,5-dihydroxy-N-pentadecylbenzamide
Homo sapiens
pH and temperature not specified in the publication
0.000027
4-cyclohexylbutyl-N-[(S)-2-oxoazetidin-3-yl]carbamate
Homo sapiens
pH and temperature not specified in the publication
0.000073
4-cyclohexylbutyl-N-[(S)-2-oxoazetidin-3-yl]carbamate
Homo sapiens
pH 7.4, 37°C
0.0000072
5-((biphenyl-4-yl)methyl)-N,N-dimethyl-2H-tetrazole-2-carboxamide
Homo sapiens
recombinant enzyme with substrate N-palmitoylethanolamine, pH not specified in the publication, 37°C
0.0000077
5-((biphenyl-4-yl)methyl)-N,N-dimethyl-2H-tetrazole-2-carboxamide
Homo sapiens
recombinant enzyme with substrate N-(4-methyl coumarin)palmitamide, pH not specified in the publication, 37°C
0.0017
N-benzyloxycarbonyl-L-serine beta-lactone
Homo sapiens
recombinant enzyme with substrate N-(4-methyl coumarin)palmitamide, pH not specified in the publication, 37°C
0.0019
N-benzyloxycarbonyl-L-serine beta-lactone
Homo sapiens
recombinant enzyme with substrate N-palmitoylethanolamine, pH not specified in the publication, 37°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
the total levels of NAAA mRNAs in androgen-sensitive cells like LNCaP are higher than those in androgen-insensitive cells
additional information
additional information
all cell types examined express NAAA but its expression levels vary by cell type, expression patterns of splicing variants a1, a2, b2, and c2, overview. Splicing variants a1 and b2 show the highest and lowest expression levels, respectively, among the four variants in all of the prostate cells and other human cells
additional information
N-acylethanolamine acid amidase is expressed at high levels in immune cells
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
proposed membrane interactions via hydrophobic helices alpha3 and alpha6
the enzyme is believed to be transported by the mannose-6-phosphate pathway to the acidic late endosomes and/or lysosomes
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
enzyme inhibitors may attenuate heat hyperalgesia and mechanical allodynia caused by local inflammation or nerve damage in animal models of pain and inflammation
physiological function
additional information
evolution
the enzyme is a cysteine amidase that belongs to the N-terminal nucleophile (Ntn) family of enzymes and is characterized by a conserved amino acid catalytic triad Cys, Arg, and Asp
evolution
the enzyme is a cysteine hydrolase belonging to the N-terminalnucleophile (Ntn) family of enzymes
physiological function
N-acylethanolamine-hydrolyzing acid amidase is a lysosomal enzyme that primarily degrades palmitoylethanolamine, a lipid amide that inhibits inflammatory responses
physiological function
the enzyme intracellularly breaks down the analgesic and anti-inflammatory mediator palmitoylethanolamide
physiological function
important role for NAAA in cell migration and in inducing tumor cell death promoting this enzyme as pharmacological target against bladder cancer
physiological function
N-acylethanolamine acid amidase (NAAA) is a lysosomal cysteine hydrolase involved in the degradation of saturated and monounsaturated fatty acid ethanolamides (FAEs), a family of endogenous lipid signaling molecules that includes oleoylethanolamide (OEA) and palmitoylethanolamide (PEA)
physiological function
the enzyme is implicated in osteoarthritis progression
additional information
the catalytic triad, is formed by cysteine, aspartate and arginine
additional information
residues Leu325 and Thr335 are catalytically important for isozyme A, and the latter one is indispensable for the enzyme activity of NAAA
additional information
the enzyme must disrupt the membrane to reach its embedded substrate, and helices alpha3 and alpha6 are likely candidates for this function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). NAAA_HUMAN
359
1
40066
Swiss-Prot
Secretory Pathway (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10972
1 * 10972, deglycosylated alpha-subunit, + 1 * 29659, deglycosylated beta-subunit, mass spectrometry, 1 * 14600 + 1 * 33000, alpha/beta heterodimer, SDS-PAGE
14600
1 * 10972, deglycosylated alpha-subunit, + 1 * 29659, deglycosylated beta-subunit, mass spectrometry, 1 * 14600 + 1 * 33000, alpha/beta heterodimer, SDS-PAGE
29659
1 * 10972, deglycosylated alpha-subunit, + 1 * 29659, deglycosylated beta-subunit, mass spectrometry, 1 * 14600 + 1 * 33000, alpha/beta heterodimer, SDS-PAGE
33000
1 * 10972, deglycosylated alpha-subunit, + 1 * 29659, deglycosylated beta-subunit, mass spectrometry, 1 * 14600 + 1 * 33000, alpha/beta heterodimer, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
x * 26300, recombinant untagged isozyme A, SDS-PAGE, x * 24200, isozyme B, SDS-PAGE, x * 222000, isozyme C, SDS-PAGE
heterodimer
1 * 10972, deglycosylated alpha-subunit, + 1 * 29659, deglycosylated beta-subunit, mass spectrometry, 1 * 14600 + 1 * 33000, alpha/beta heterodimer, SDS-PAGE
heterotetramer
enzyme NAAA adopts an alphabetabetaalpha-fold with a helical alpha-subunit
additional information
tryptic digestion and MALDI-TOF mass spectrometry fingerprinting gives evidence for the lack of a disulfide bond between subunits
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
proteolytic modification
glycoprotein
4 glycosylation sites Asn37, Asn107, Asn309, and Asn333, N-linked oligosaccharides of approximately 1500 Da, all cleavable by peptide-N-glycosidase F
proteolytic modification
the glycoprotein undergoes removal of an N-terminal signal peptide after biosynthesis. Autocatalytic acid cleavage of the zymogen into alpha- and beta-subunits (14.6 and 33.3 kDa) activates the enzyme. Cys126 is essential for the proteolytic cleavage of the pro-enzyme
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinnat enzyme C116A mutant in complex with ARN19702 and in presence of Triton X-100, X-ray diffraction structure determination and analysis at 3.0 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C116A
site-directed mutagenesis, inhibition of disulfide bridge formation
L325A
site-directed mutagenesis of isozyme A, the mutant shows reduced activity compared to wild-type
L325T
site-directed mutagenesis of isozyme A, the mutant shows reduced activity compared to wild-type
N112S
site-directed mutagenesis, the mutation abolishes an N-linked glycosylation site
N338S
site-directed mutagenesis, the mutation abolishes an N-linked glycosylation site4
T335A
site-directed mutagenesis of isozyme A, the mutant is almost inactive
T335V
site-directed mutagenesis of isozyme A, the mutant is almost inactive
additional information
selective alkylation of the enzyme's cysteine residues results in almost complete loss of activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant C-terminally His6-tagged enzyme from HEK-293 cells by nickel affinity chromatography
recombinant His6-tagged wild-type and mutant enzymes from Spodoptera frugiperda Sf9 insect cells by nickel affinity chromatography, gel filtration, and anion exchange chromatography
recombinant His6-tagged zymogen from HEK-293 cells by ammonium sulfate fractionation, dialysis, metal affinity chromatography, and again dialysis followed by ultrafiltration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene NAAA, genotyping, six splice variants (a1, b1, c1, a2, b2, and c2), whereof four major splice variants (a1, a2, b2, and c2) are identified in a human prostate cancer cell line LNCaP, they are composed of exons 1-11, exons 1-10 and 12, exons 1-9 and 12, and exons 1-8 and 12, respectively, quantitative PCR expression analysis, method development for individual quantification. Variants a1 and a2 encode the same full-length NAAA protein, which is catalytically active, while b2 and c2 are translated to C-terminally truncated proteins. Recombinant expression in HEK-293 cells. The truncated forms are detected as catalytically inactive precursor proteins, but not as mature forms, expression of N-terminally FLAG-tagged isoform A of human NAAA, corresponding to splice variant a1, in HEK-293 cells. The mature enzyme form loses the N-terminal FLAG tag
recombinant expression of the C-terminally His6-tagged enzyme in HEK-293 cells
recombinant expression of wild-type and mutant enzymes NAAA in Spodoptera frugiperda Sf9 insect cells via baculovirus transfection method, the enzyme is secreted. The endogenous signal peptide comprising the first 28-33 residues is replaced by the melittin signal peptide MKFLVNVALVFMVVYISYIYA followed by a His6-tag DRHHHHHHKL. Constructs encompassed residues 29-359 of NAAA of human enzyme
recombinant stable expression of the His6-tagged zymogen in HEK-293 cells, ammonium chloride treatment stimulates secretion of the lysosomal proteins from the HEK293 cells
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
medicine
modulation of the tissue levels of palmitoylethanolamide by inhibition of enzymes responsible for the breakdown of this lipid mediator, including the N-acylethanolamine acid amidase, may represent therefore a therapeutic strategy for the treatment of pain and inflammation
pharmacology
drug development
inhibitors against N-acylethanolamine-hydrolyzing acid amidase are promising tools against bladder cancer
drug development
the cysteine hydrolase, N-acylethanolamine acid amidase (NAAA) is a promising target for analgesic and anti-inflammatory drugs
pharmacology
potential of blocking N-acylethanolamines like palmitoylethanolamide or N-arachidonlyethanolamine (anandamide) from enzymatic degradation via enzyme inhibition as a strategy for pain treatment
pharmacology
NAAA inhibitor F215 is a therapeutic agent for osteoarthritis. The therapeutic effects of F215 are blocked by the PPAR-alpha antagonist MK886
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hansen, H.; Lauritzen, L.; Moesgaard, B.; Strand, A.M.; Hansen, H.
Formation of N-acyl-phoshatidylethanolamines and N-acylethanolamines: proposed role in neurotoxicity
Biochem. Pharmacol.
55
719-725
1998
Homo sapiens, Mus sp., Rattus norvegicus
Fiasella, A.; Nuzzi, A.; Summa, M.; Armirotti, A.; Tarozzo, G.; Tarzia, G.; Mor, M.; Bertozzi, F.; Bandiera, T.; Piomelli, D.
3-Aminoazetidin-2-one derivatives as N-acylethanolamine acid amidase (NAAA) inhibitors suitable for systemic administration
ChemMedChem
9
1602-1614
2014
Homo sapiens (Q02083)
West, J.; Zvonok, N.; Whitten, K.; Wood, J.; Makriyannis, A.
Mass spectrometric characterization of human N-acylethanolamine-hydrolyzing acid midase
J. Proteome Res.
11
972-981
2012
Homo sapiens (Q02083)
Bandiera, T.; Ponzano, S.; Piomelli, D.
Advances in the discovery of N-acylethanolamine acid amidase inhibitors
Pharmacol. Res.
86
11-17
2014
Homo sapiens (Q02083), Mus musculus, Rattus norvegicus (Q5KTC7)
West, J.M.; Zvonok, N.; Whitten, K.M.; Vadivel, S.K.; Bowman, A.L.; Makriyannis, A.
Biochemical and mass spectrometric characterization of human N-acylethanolamine-hydrolyzing acid amidase inhibition
PLoS ONE
7
e43877
2012
Homo sapiens (Q02083), Homo sapiens
Ribeiro, A.; Pontis, S.; Mengatto, L.; Armirotti, A.; Chiurchiu, V.; Capurro, V.; Fiasella, A.; Nuzzi, A.; Romeo, E.; Moreno-Sanz, G.; Maccarrone, M.; Reggiani, A.; Tarzia, G.; Mor, M.; Bertozzi, F.; Bandiera, T.; Piomelli, D.
A potent systemically active N-acylethanolamine acid amidase inhibitor that suppresses inflammation and human macrophage activation
ACS Chem. Biol.
10
1838-1846
2015
Homo sapiens (Q02083), Mus musculus (Q9D7V9), Mus musculus C57BL/6J (Q9D7V9), Rattus norvegicus (Q5KTC7)
Romeo, E.; Ponzano, S.; Armirotti, A.; Summa, M.; Bertozzi, F.; Garau, G.; Bandiera, T.; Piomelli, D.
Activity-based probe for N-acylethanolamine acid amidase
ACS Chem. Biol.
10
2057-2064
2015
Homo sapiens (Q02083), Rattus norvegicus (Q5KTC7), Rattus norvegicus Sprague-Dawley (Q5KTC7)
Sakura, Y.; Tsuboi, K.; Uyama, T.; Zhang, X.; Taoka, R.; Sugimoto, M.; Kakehi, Y.; Ueda, N.
A quantitative study on splice variants of N-acylethanolamine acid amidase in human prostate cancer cells and other cells
Biochim. Biophys. Acta
1861
1951-1958
2016
Homo sapiens (Q02083)
Vago, R.; Bettiga, A.; Salonia, A.; Ciuffreda, P.; Ottria, R.
Development of new inhibitors for N-acylethanolamine-hydrolyzing acid amidase as promising tool against bladder cancer
Bioorg. Med. Chem.
25
1242-1249
2017
Homo sapiens (Q02083)
Petracca, R.; Romeo, E.; Baggelaar, M.P.; Artola, M.; Pontis, S.; Ponzano, S.; Overkleeft, H.S.; van der Stelt, M.; Piomelli, D.
Novel activity-based probes for N-acylethanolamine acid amidase
Chem. Commun. (Camb.)
53
11810-11813
2017
Homo sapiens (Q02083)
Sagheddu, C.; Scherma, M.; Congiu, M.; Fadda, P.; Carta, G.; Banni, S.; Wood, J.T.; Makriyannis, A.; Malamas, M.S.; Pistis, M.
Inhibition of N-acylethanolamine acid amidase reduces nicotine-induced dopamine activation and reward
Neuropharmacology
144
327-336
2019
Homo sapiens (Q02083), Rattus norvegicus (Q6P7S1), Rattus norvegicus Sprague-Dawley (Q6P7S1)
Zhou, P.; Xiang, L.; Yang, Y.; Wu, Y.; Hu, T.; Liu, X.; Lin, F.; Xiu, Y.; Wu, K.; Lu, C.; Ren, J.; Qiu, Y.; Li, Y.
N-Acylethanolamine acid amidase (NAAA) inhibitor F215 as a novel therapeutic agent for osteoarthritis
Pharmacol. Res.
145
104264
2019
Homo sapiens (Q02083), Rattus norvegicus (Q5KTC7)
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