PMID: 30301806

 

    Legend: Gene, Sites

Title : Molecular mechanism of activation of the immunoregulatory amidase NAAA

Abstract :

1. Palmitoylethanolamide is a bioactive lipid that strongly alleviates pain and inflammation in animal models and in humans
2. Its signaling activity is terminated through degradation by N-acylethanolamine acid amidase ( NAAA ), a cysteine hydrolase expressed at high levels in immune cells
3. Pharmacological inhibitors of NAAA activity exert profound analgesic and antiinflammatory effects in rodent models, pointing to this protein as a potential target for therapeutic drug discovery
4. To facilitate these efforts and to better understand the molecular mechanism of action of NAAA , we determined crystal structures of this enzyme in various activation states and in complex with several ligands, including both a covalent and a reversible inhibitor
5. Self-proteolysis exposes the otherwise buried active site of NAAA to allow catalysis
6. Formation of a stable substrate- or inhibitor-binding site appears to be conformationally coupled to the interaction of a pair of hydrophobic helices in the enzyme with lipid membranes, resulting in the creation of a linear hydrophobic cavity near the active site that accommodates the ligand's acyl chain

Output (sent_index, trigger, protein, sugar, site):

Output(Part-Of) (sent_index, protein, site):

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
N-acylethanolamine acid amidase	27163	2