Target Information
| Target General Information | Top | |||||
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| Target ID |
T78326
(Former ID: TTDI00195)
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| Target Name |
N-acylethanolamine-hydrolyzing acidamidase (NAAA)
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| Synonyms |
Nacylsphingosine amidohydrolaselike; Nacylethanolaminehydrolyzing acid amidase subunit beta; NAAA; Acid ceramidaselike protein; ASAHlike protein
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| Gene Name |
NAAA
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Degrades bioactive fatty acid amides to their corresponding acids, with the following preference: N- palmitoylethanolamine > N-myristoylethanolamine > N- lauroylethanolamine = N-stearoylethanolamine > N- arachidonoylethanolamine > N-oleoylethanolamine. Also exhibits weak hydrolytic activity against the ceramides N- lauroylsphingosine and N-palmitoylsphingosine.
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| BioChemical Class |
Carbon-nitrogen hydrolase
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| UniProt ID | ||||||
| EC Number |
EC 3.5.1.-
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| Sequence |
MRTADREARPGLPSLLLLLLAGAGLSAASPPAAPRFNVSLDSVPELRWLPVLRHYDLDLV
RAAMAQVIGDRVPKWVHVLIGKVVLELERFLPQPFTGEIRGMCDFMNLSLADCLLVNLAY ESSVFCTSIVAQDSRGHIYHGRNLDYPFGNVLRKLTVDVQFLKNGQIAFTGTTFIGYVGL WTGQSPHKFTVSGDERDKGWWWENAIAALFRRHIPVSWLIRATLSESENFEAAVGKLAKT PLIADVYYIVGGTSPREGVVITRNRDGPADIWPLDPLNGAWFRVETNYDHWKPAPKEDDR RTSAIKALNATGQANLSLEALFQILSVVPVYNNFTIYTTVMSAGSPDKYMTRIRNPSRK Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: 2-{2-[4-(1,1,3,3-Tetramethylbutyl)phenoxy]ethoxy}ethanol | Ligand Info | |||||
| Structure Description | Human N-acylethanolamine-hydrolyzing acid amidase (NAAA) in complex with non-covalent benzothiazole-piperazine inhibitor ARN19702, in presence of Triton X-100 | PDB:6DXX | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [3] |
| PDB Sequence |
> Chain A
SPPAAPRFNV 38 SLDSVPELRW48 LPVLRHYDLD58 LVRAAMAQVI68 GDRVPKWVHV78 LIGKVVLELE 88 RFLPQPFTGE98 IRGMCDFMNL108 SLADCLLVNL118 AYESSVF> Chain B CTSIVAQDSR 135 GHIYHGRNLD145 YPFGNVLRKL155 TVDVQFLKNG165 QIAFTGTTFI175 GYVGLWTGQS 185 PHKFTVSGDE195 RDKGWWWENA205 IAALFRRHIP215 VSWLIRATLS225 ESENFEAAVG 235 KLAKTPLIAD245 VYYIVGGTSP255 REGVVITRNR265 DGPADIWPLD275 PLNGAWFRVE 285 TNYDHWKPAP295 KEDDRRTSAI305 KALNATGQAN315 LSLEALFQIL325 SVVPVYNNFT 335 IYTTVMSAGS345 PDKYMTRIRN355 P
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PRO73[A]
2.127
TRP75[A]
1.974
VAL76[A]
2.433
LEU79[A]
2.122
ILE80[A]
3.181
VAL83[A]
3.275
LEU87[A]
2.324
PHE90[A]
4.473
LEU115[A]
3.513
LEU118[A]
2.224
GLU121[A]
2.382
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| Ligand Name: [2-(ethylsulfonyl)phenyl][(2S)-4-(6-fluoro-1,3-benzothiazol-2-yl)-2-methylpiperazin-1-yl]methanone | Ligand Info | |||||
| Structure Description | Human N-acylethanolamine-hydrolyzing acid amidase (NAAA) in complex with non-covalent benzothiazole-piperazine inhibitor ARN19702, in presence of Triton X-100 | PDB:6DXX | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [3] |
| PDB Sequence |
> Chain A
SPPAAPRFNV 38 SLDSVPELRW48 LPVLRHYDLD58 LVRAAMAQVI68 GDRVPKWVHV78 LIGKVVLELE 88 RFLPQPFTGE98 IRGMCDFMNL108 SLADCLLVNL118 AYESSVF> Chain B CTSIVAQDSR 135 GHIYHGRNLD145 YPFGNVLRKL155 TVDVQFLKNG165 QIAFTGTTFI175 GYVGLWTGQS 185 PHKFTVSGDE195 RDKGWWWENA205 IAALFRRHIP215 VSWLIRATLS225 ESENFEAAVG 235 KLAKTPLIAD245 VYYIVGGTSP255 REGVVITRNR265 DGPADIWPLD275 PLNGAWFRVE 285 TNYDHWKPAP295 KEDDRRTSAI305 KALNATGQAN315 LSLEALFQIL325 SVVPVYNNFT 335 IYTTVMSAGS345 PDKYMTRIRN355 P
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LEU59[A]
4.583
VAL60[A]
2.192
ARG61[A]
4.519
ALA63[A]
2.225
MET64[A]
2.378
VAL67[A]
3.453
MET106[A]
4.932
VAL116[A]
3.027
ASN117[A]
4.281
ALA119[A]
2.622
TYR120[A]
2.415
SER123[A]
4.756
PHE125[A]
2.732
CYS126[B]
3.429
ARG142[B]
4.081
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Similarity Proteins
Human Tissue Distribution
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | Dopamine receptor mediated signaling pathway | |||||
| References | Top | |||||
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| REF 1 | Selective N-acylethanolamine-hydrolyzing acid amidase inhibition reveals a key role for endogenous palmitoylethanolamide in inflammation. Proc Natl Acad Sci U S A. 2009 Dec 8;106(49):20966-71. | |||||
| REF 2 | N-cyclohexanecarbonylpentadecylamine: a selective inhibitor of the acid amidase hydrolysing N-acylethanolamines, as a tool to distinguish acid amidase from fatty acid amide hydrolase. Biochem J. 2004Apr 1;379(Pt 1):99-106. | |||||
| REF 3 | Molecular mechanism of activation of the immunoregulatory amidase NAAA. Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):E10032-E10040. | |||||
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