6dy0: Difference between revisions
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<StructureSection load='6dy0' size='340' side='right'caption='[[6dy0]], [[Resolution|resolution]] 3.01Å' scene=''> | <StructureSection load='6dy0' size='340' side='right'caption='[[6dy0]], [[Resolution|resolution]] 3.01Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6dy0]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6dy0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DY0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DY0 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=HJA:( | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.014Å</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=HJA:(2~{S})-3-azanyl-2-(4-cyclohexylbutoxycarbonylamino)propanethioic+S-acid'>HJA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TON:2-{2-[4-(1,1,3,3-TETRAMETHYLBUTYL)PHENOXY]ETHOXY}ETHANOL'>TON</scene></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=6dy0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dy0 OCA], [https://pdbe.org/6dy0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dy0 RCSB], [https://www.ebi.ac.uk/pdbsum/6dy0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dy0 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/NAAA_RABIT NAAA_RABIT] Degrades bioactive fatty acid amides to their corresponding acids, with the following preference: N-palmitoylethanolamine > N-myristoylethanolamine > N-stearoylethanolamine > N-oleoylethanolamine > N-linoleoylethanolamine > N-arachidonoylethanolamine.[UniProtKB:Q5KTC7] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Gebai | [[Category: Oryctolagus cuniculus]] | ||
[[Category: Gorelik | [[Category: Gebai A]] | ||
[[Category: Illes | [[Category: Gorelik A]] | ||
[[Category: Nagar | [[Category: Illes K]] | ||
[[Category: Piomelli | [[Category: Nagar B]] | ||
[[Category: Piomelli D]] | |||
Latest revision as of 11:59, 9 October 2024
Rabbit N-acylethanolamine-hydrolyzing acid amidase (NAAA) covalently bound to beta-lactam inhibitor ARN726, in presence of Triton X-100Rabbit N-acylethanolamine-hydrolyzing acid amidase (NAAA) covalently bound to beta-lactam inhibitor ARN726, in presence of Triton X-100
Structural highlights
FunctionNAAA_RABIT Degrades bioactive fatty acid amides to their corresponding acids, with the following preference: N-palmitoylethanolamine > N-myristoylethanolamine > N-stearoylethanolamine > N-oleoylethanolamine > N-linoleoylethanolamine > N-arachidonoylethanolamine.[UniProtKB:Q5KTC7] Publication Abstract from PubMedPalmitoylethanolamide 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
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