View source for N-acylethanolamine-hydrolyzing acid amidase (Mus musculus)

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{{#invoke:InfoboxforTarget|run|ASAH-like protein, NAAA|[https://www.uniprot.org/uniprot/Q9D7V9 Q9D7V9]|Mus musculus|Cys131|[http://pfam.xfam.org/family/PF02275 Linear amide C-N hydrolases, choloylglycine hydrolase family],<br/>Acid ceramidase family|[[:Category:N-acylethanolamine-hydrolyzing acid amidase (Mus musculus)|Ligand list]]|Metabolic enzyme}}
==Summary==

===Protein Function ===
NAAA must operate under acidic conditions (pH ~4.5), and is completely inactivated at a pH of 8. Selective inhibitors of NAAA are ester and amide compounds, such as N-cyclohexanecarbonylpentadecylamine. NAAA is cleaved proteolytically at residue Cys126. NAAA cleaves C-N non-peptide bonds in linear amides, particularly ethanolamides. Its mechanism is quite similar to that of AC, which is further supported by AC's ability to cleave N-acylethanolamines (NAEs), albeit at far lower rates and with different specificities. While mechanistic details are not very well known, catalytic activity of NAAA is thought to be activated by Cys126 and Asp145.<br/>
Fatty acid ethanolamines (FAEs) perform several physiological functions, most notably serving as messengers for pain and inflammation. NAAA's are found primarily in the lysosomal compartment of macrophages, in line with most inflammation-related proteins. They perform FAE hydrolysis, the final step in the signaling cascade for pain and inflammation, yielding an ethanolamine and a fatty acid. While it processes the cleavage of many different substrates, NAAA is most active with the substrate N-palmitoylethanolamine, suggesting that this is one of the key messengers of pain. (From Wikipedia)<br/><br/>
[[File:551-function.jpg|center|500px]]
<div align="center">Mechanism for the hydrolysis of ethanolamides by NAAA</div><br/>
===Cys Function & Property===
Cys131 is the active site of mouse NAAA. <br/>
:[[File:152.png|center|600px]]
<div align="center">Alignment of NAAA from different species</div><br/>

* Hydrophobic property:
:[[File:553-hydro.png||600px]]
* SASA：
:Cys131: Unknown<br/>

==Protein Sequence==
<font face="Courier">
MGTLATRAAC HGAHLALALL LLLSLSGPWL SAVVPGTPPL FNVSLDAAPE <br/>
QRWLPMLRHY DPDFLRTAVA QVIGDRVPQW VLGMVGEIVS KVESFLPQPF <br/>
TDEIRSICDS LNLSLADGIL VNLAYEASAF <span style="background:#ffff00">'''C'''</span>TSIVAQDSQ GHIYHGRNLD <br/>
YPFGKILRKL TANVQFIKNG QIAFTGTTFV GYVGLWTGQS PHKFTISGDE <br/>
RDKGWWWENM IAALSLGHSP ISWLIRKTLS ESESFEAAVY TLAKTPLIAD <br/>
VYYIVGGTSP KEGVVITRDR GGPADIWPLD PLNGEWFRVE TNYDHWKPAP <br/>
KVDDRRTPAI KALNATGQAH LNLETLFQVL SLFPVYNNYT IYTTVMSAAE <br/>
PDKYLTMIRN PS            <br/> 
</font>

==Structural Information==
*Known structure with covalent ligand: <br/>
:Unknown<br/>

*Protein structure:
:Unknown<br/>

==Related Pathway==
:Unknown <br/>

==Experimental Evidence==
:Cys-directed Mutation, Homologous Analysis Of Sequence 

==Reference==
# Armirotti A, Romeo E, Ponzano S, et al. '''β-Lactones inhibit N-acylethanolamine acid amidase by S-acylation of the catalytic N-terminal cysteine[J].''' ACS medicinal chemistry letters, 2012, 3(5): 422-426. [https://www.ncbi.nlm.nih.gov/pubmed/?term=24900487 24900487]<br/> 
# Solorzano C, Zhu C, Battista N, et al. '''Selective N-acylethanolamine-hydrolyzing acid amidase inhibition reveals a key role for endogenous palmitoylethanolamide in inflammation[J].''' Proceedings of the National Academy of Sciences, 2009, 106(49): 20966-20971. [https://www.ncbi.nlm.nih.gov/pubmed/?term=19926854 19926854]

[[Category:Targets]]
[[Category:Homo sapiens]]
[[Category:Metabolic enzyme]]
[[Category:Acid ceramidase family]]