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N-Acylphosphatidylethanolamine-phospholipase D

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Target id: 1398

Nomenclature: N-Acylphosphatidylethanolamine-phospholipase D

Abbreviated Name: NAPE-PLD

Family: N-Acylethanolamine turnover

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 393 7q22.1 NAPEPLD N-acyl phosphatidylethanolamine phospholipase D
Mouse - 396 5 A3 Napepld N-acyl phosphatidylethanolamine phospholipase D
Rat - 396 4q11 Napepld N-acyl phosphatidylethanolamine phospholipase D
Previous and Unofficial Names Click here for help
chromosome 7 open reading frame 18, N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D | FMP30
Database Links Click here for help
Alphafold
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of NAPE-PLD in complex with 1,3,7-Naphthalenetrisulfonic acid
PDB Id:  8P96
Ligand:  N3SA
Resolution:  2.86Å
Species:  Human
References:  3
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of NAPE-PLD in complex with hydrochlorothiazide
PDB Id:  8PC4
Ligand:  hydrochlorothiazide
Resolution:  2.85Å
Species:  Human
References:  3
Enzyme Reaction Click here for help
EC Number: 3.1.4.54

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
LEI-401 Small molecule or natural product Hs Inhibition 7.6 pKi 4
pKi 7.6 (Ki 2.7x10-8 M) [4]
Description: hNAPE-PLD in vitro activity assay.
hexachlorophene Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibition 5.0 pIC50 1
pIC50 5.0 (IC50 9.8x10-6 M) [1]
bithionol Small molecule or natural product Ligand has a PDB structure Hs Inhibition 5.0 pIC50 1
pIC50 5.0 (IC50 1.07x10-5 M) [1]
ARN19874 Small molecule or natural product Hs Inhibition 4.5 pIC50 2
pIC50 4.5 (IC50 3.37x10-5 M) [2]
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
N3SA Small molecule or natural product Ligand has a PDB structure Hs Binding 7.5 pKd 3
pKd 7.5 (Kd 3.3x10-8 M) [3]
Description: Equilibrium dissociation constant determined in the presence of DCA
indapamide Small molecule or natural product Approved drug Hs Binding 6.2 pKd 3
pKd 6.2 (Kd 5.7x10-7 M) [3]
Description: Equilibrium dissociation constant determined in the presence of DCA
chlorthalidone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Binding 6.2 pKd 3
pKd 6.2 (Kd 6.8x10-7 M) [3]
Description: Equilibrium dissociation constant determined in the presence of DCA
hydrochlorothiazide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Binding 5.1 – 6.1 pKd 3
pKd 6.1 (Kd 7.4x10-7 M) [3]
Description: equilibrium dissociation constant in presence of deoxycholic acid, determined by SPR
pKd 5.1 (Kd 8x10-6 M) [3]
Description: Determined by surface plasmon resonance, in the absence of deoxycholic acid in the bile acid binding domain
Allosteric Modulator Comments
Thiazide and thiazide-like drugs mediate allosteric stabilization of NAPE-PLD dimers [3]. This mechanism contributes directly to thiazide-induced reduction in vascular resistance, in additional to their established diuretic effect via inhibition of the Na-Cl symporter (SLC12A3).
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation

References

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1. Aggarwal G, Zarrow JE, Mashhadi Z, Flynn CR, Vinson P, Weaver CD, Davies SS. (2020) Symmetrically substituted dichlorophenes inhibit N-acyl-phosphatidylethanolamine phospholipase D. J Biol Chem, 295 (21): 7289-7300. [PMID:32284327]

2. Castellani B, Diamanti E, Pizzirani D, Tardia P, Maccesi M, Realini N, Magotti P, Garau G, Bakkum T, Rivara S et al.. (2017) Synthesis and characterization of the first inhibitor of N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD). Chem Commun (Camb.), 53 (95): 12814-12817. [PMID:29143042]

3. Chiarugi S, Margheriti F, De Lorenzi V, Martino E, Margheritis EG, Moscardini A, Marotta R, Chaves-Sanjuan A, Del Seppia C, Federighi G et al.. (2025) NAPE-PLD is target of thiazide diuretics. Cell Chem Biol, [Epub ahead of print]. [PMID:39999832]

4. Mock ED, Mustafa M, Gunduz-Cinar O, Cinar R, Petrie GN, Kantae V, Di X, Ogasawara D, Varga ZV, Paloczi J et al.. (2020) Discovery of a NAPE-PLD inhibitor that modulates emotional behavior in mice. Nat Chem Biol, 16 (6): 667-675. [PMID:32393901]

Contributors

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