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| | <StructureSection load='5w7a' size='340' side='right'caption='[[5w7a]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='5w7a' size='340' side='right'caption='[[5w7a]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5w7a]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/European_rabbit European rabbit]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W7A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W7A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5w7a]] 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=5W7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W7A FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FTT:3-HYDROXY-TETRADECANOIC+ACID'>FTT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AOAH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 European rabbit])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FTT:3-HYDROXY-TETRADECANOIC+ACID'>FTT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acyloxyacyl_hydrolase Acyloxyacyl hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.77 3.1.1.77] </span></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=5w7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w7a OCA], [https://pdbe.org/5w7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w7a RCSB], [https://www.ebi.ac.uk/pdbsum/5w7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w7a ProSAT]</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=5w7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w7a OCA], [http://pdbe.org/5w7a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w7a RCSB], [http://www.ebi.ac.uk/pdbsum/5w7a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w7a ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AOAH_RABIT AOAH_RABIT]] Removes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (LPS). By breaking down LPS, terminates the host response to bacterial infection and prevents prolonged and damaging inflammatory responses. In peritoneal macrophages, seems to be important for recovery from a state of immune tolerance following infection by Gram-negative bacteria.[UniProtKB:O35298] | + | [https://www.uniprot.org/uniprot/AOAH_RABIT AOAH_RABIT] Removes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (LPS). By breaking down LPS, terminates the host response to bacterial infection and prevents prolonged and damaging inflammatory responses. In peritoneal macrophages, seems to be important for recovery from a state of immune tolerance following infection by Gram-negative bacteria.[UniProtKB:O35298] |
| | <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: Acyloxyacyl hydrolase]] | |
| - | [[Category: European rabbit]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gorelik, A]] | + | [[Category: Oryctolagus cuniculus]] |
| - | [[Category: Illes, K]] | + | [[Category: Gorelik A]] |
| - | [[Category: Nagar, B]] | + | [[Category: Illes K]] |
| - | [[Category: Gdsl esterase]] | + | [[Category: Nagar B]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Lipopolysaccharide]]
| + | |
| - | [[Category: Lp]]
| + | |
| - | [[Category: Saposin]]
| + | |
| Structural highlights
5w7a is a 2 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.3Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
AOAH_RABIT Removes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (LPS). By breaking down LPS, terminates the host response to bacterial infection and prevents prolonged and damaging inflammatory responses. In peritoneal macrophages, seems to be important for recovery from a state of immune tolerance following infection by Gram-negative bacteria.[UniProtKB:O35298]
Publication Abstract from PubMed
LPS is a potent bacterial endotoxin that triggers the innate immune system. Proper recognition of LPS by pattern-recognition receptors requires a full complement of typically six acyl chains in the lipid portion. Acyloxyacyl hydrolase (AOAH) is a host enzyme that removes secondary (acyloxyacyl-linked) fatty acids from LPS, rendering it immunologically inert. This activity is critical for recovery from immune tolerance that follows Gram-negative infection. To understand the molecular mechanism of AOAH function, we determined its crystal structure and its complex with LPS. The substrate's lipid moiety is accommodated in a large hydrophobic pocket formed by the saposin and catalytic domains with a secondary acyl chain inserted into a narrow lateral hydrophobic tunnel at the active site. The enzyme establishes dispensable contacts with the phosphate groups of LPS but does not interact with its oligosaccharide portion. Proteolytic processing allows movement of an amphipathic helix possibly involved in substrate access at membranes.
Crystal structure of the mammalian lipopolysaccharide detoxifier.,Gorelik A, Illes K, Nagar B Proc Natl Acad Sci U S A. 2018 Jan 17. pii: 1719834115. doi:, 10.1073/pnas.1719834115. PMID:29343645[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gorelik A, Illes K, Nagar B. Crystal structure of the mammalian lipopolysaccharide detoxifier. Proc Natl Acad Sci U S A. 2018 Jan 17. pii: 1719834115. doi:, 10.1073/pnas.1719834115. PMID:29343645 doi:http://dx.doi.org/10.1073/pnas.1719834115
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