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| | <StructureSection load='6dxy' size='340' side='right'caption='[[6dxy]], [[Resolution|resolution]] 1.85Å' scene=''> | | <StructureSection load='6dxy' size='340' side='right'caption='[[6dxy]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6dxy]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DXY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DXY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6dxy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DXY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DXY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P33:3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL'>P33</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.851Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene>, <scene name='pdbligand=P33:3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL'>P33</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Naaa, Asahl ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6dxy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dxy OCA], [https://pdbe.org/6dxy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dxy RCSB], [https://www.ebi.ac.uk/pdbsum/6dxy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dxy ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/N-(long-chain-acyl)ethanolamine_deacylase N-(long-chain-acyl)ethanolamine deacylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.60 3.5.1.60] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6dxy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dxy OCA], [http://pdbe.org/6dxy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dxy RCSB], [http://www.ebi.ac.uk/pdbsum/6dxy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dxy ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NAAA_MOUSE NAAA_MOUSE]] Degrades bioactive fatty acid amides to their corresponding acids, with a preference for N-palmitoylethanolamine. | + | [https://www.uniprot.org/uniprot/NAAA_MOUSE NAAA_MOUSE] Degrades bioactive fatty acid amides to their corresponding acids, with a preference for N-palmitoylethanolamine. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Gebai, A]] | + | [[Category: Gebai A]] |
| - | [[Category: Gorelik, A]] | + | [[Category: Gorelik A]] |
| - | [[Category: Illes, K]] | + | [[Category: Illes K]] |
| - | [[Category: Nagar, B]] | + | [[Category: Nagar B]] |
| - | [[Category: Piomelli, D]] | + | [[Category: Piomelli D]] |
| - | [[Category: Endocannabinoid]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Lipase]]
| + | |
| Structural highlights
6dxy is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.851Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
NAAA_MOUSE Degrades bioactive fatty acid amides to their corresponding acids, with a preference for N-palmitoylethanolamine.
Publication Abstract from PubMed
Palmitoylethanolamide is a bioactive lipid that strongly alleviates pain and inflammation in animal models and in humans. Its signaling activity is terminated through degradation by N-acylethanolamine acid amidase (NAAA), a cysteine hydrolase expressed at high levels in immune cells. 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. 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. Self-proteolysis exposes the otherwise buried active site of NAAA to allow catalysis. 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.
Molecular mechanism of activation of the immunoregulatory amidase NAAA.,Gorelik A, Gebai A, Illes K, Piomelli D, Nagar B Proc Natl Acad Sci U S A. 2018 Oct 9. pii: 1811759115. doi:, 10.1073/pnas.1811759115. PMID:30301806[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gorelik A, Gebai A, Illes K, Piomelli D, Nagar B. Molecular mechanism of activation of the immunoregulatory amidase NAAA. Proc Natl Acad Sci U S A. 2018 Oct 9. pii: 1811759115. doi:, 10.1073/pnas.1811759115. PMID:30301806 doi:http://dx.doi.org/10.1073/pnas.1811759115
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