View source for N-acylethanolamine-hydrolyzing acid amidase (Homo sapiens)

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{{#invoke:InfoboxforTarget|run|ASAH-like protein, NAAA|[https://www.uniprot.org/uniprot/Q02083 Q02083]|Homo sapiens|Cys126|[http://pfam.xfam.org/family/PF02275 Linear amide C-N hydrolases, choloylglycine hydrolase family],<br/>Acid ceramidase family|[[:Category:N-acylethanolamine-hydrolyzing acid amidase (Homo sapiens)|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===
Cys126 is the active site of NAAA. <br/>

* Hydrophobic property:
:[[File:551-hydro.png||600px]]
* SASA：
:Cys126: Unknown<br/>

==Protein Sequence==
<font face="Courier">
MRTADREARP GLPSLLLLLL AGAGLSAASP PAAPRFNVSL DSVPELRWLP <br/>
VLRHYDLDLV RAAMAQVIGD RVPKWVHVLI GKVVLELERF LPQPFTGEIR <br/>
GMCDFMNLSL ADCLLVNLAY ESSVF<span style="background:#ffff00">'''C'''</span>TSIV AQDSRGHIYH GRNLDYPFGN <br/>
VLRKLTVDVQ FLKNGQIAFT GTTFIGYVGL WTGQSPHKFT VSGDERDKGW <br/>
WWENAIAALF RRHIPVSWLI RATLSESENF EAAVGKLAKT PLIADVYYIV <br/>
GGTSPREGVV ITRNRDGPAD IWPLDPLNGA WFRVETNYDH WKPAPKEDDR <br/>
RTSAIKALNA TGQANLSLEA LFQILSVVPV YNNFTIYTTV MSAGSPDKYM <br/>
TRIRNPSRK          <br/> 
</font>

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

*Protein structure:
:Unknown<br/>

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

==Experimental Evidence==
:MS/MS Spectra, Extracted Ion Chromatogram, Tryptic Digest, MALDI-TOF/MS, Homology Modeling

==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/> 
# West J M, Zvonok N, Whitten K M, et al. '''Biochemical and mass spectrometric characterization of human N-acylethanolamine-hydrolyzing acid amidase inhibition[J].''' PLoS One, 2012, 7(8): e43877. [https://www.ncbi.nlm.nih.gov/pubmed/?term=22952796 22952796]<br/>

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