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| | ==Human acyloxyacyl hydrolase (AOAH), proteolytically processed, S263A mutant, with LPS== | | ==Human acyloxyacyl hydrolase (AOAH), proteolytically processed, S263A mutant, with LPS== |
| - | <StructureSection load='5w7c' size='340' side='right' caption='[[5w7c]], [[Resolution|resolution]] 2.23Å' scene=''> | + | <StructureSection load='5w7c' size='340' side='right'caption='[[5w7c]], [[Resolution|resolution]] 2.23Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5w7c]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W7C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W7C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5w7c]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W7C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W7C 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=DAO:LAURIC+ACID'>DAO</scene>, <scene name='pdbligand=FTT:3-HYDROXY-TETRADECANOIC+ACID'>FTT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 2.23Å</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=9606 HUMAN])</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=DAO:LAURIC+ACID'>DAO</scene>, <scene name='pdbligand=FTT:3-HYDROXY-TETRADECANOIC+ACID'>FTT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=5w7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w7c OCA], [https://pdbe.org/5w7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w7c RCSB], [https://www.ebi.ac.uk/pdbsum/5w7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w7c 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=5w7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w7c OCA], [http://pdbe.org/5w7c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w7c RCSB], [http://www.ebi.ac.uk/pdbsum/5w7c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w7c ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AOAH_HUMAN AOAH_HUMAN]] Removes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (PubMed:1883828, PubMed:8089145). By breaking down LPS, terminates the host response to bacterial infection and prevents prolonged and damaging inflammatory responses (By similarity). In peritoneal macrophages, seems to be important for recovery from a state of immune tolerance following infection by Gram-negative bacteria (By similarity).[UniProtKB:O35298]<ref>PMID:1883828</ref> <ref>PMID:8089145</ref> | + | [https://www.uniprot.org/uniprot/AOAH_HUMAN AOAH_HUMAN] Removes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (PubMed:1883828, PubMed:8089145). By breaking down LPS, terminates the host response to bacterial infection and prevents prolonged and damaging inflammatory responses (By similarity). In peritoneal macrophages, seems to be important for recovery from a state of immune tolerance following infection by Gram-negative bacteria (By similarity).[UniProtKB:O35298]<ref>PMID:1883828</ref> <ref>PMID:8089145</ref> |
| | <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: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Gorelik, A]] | + | [[Category: Gorelik A]] |
| - | [[Category: Illes, K]] | + | [[Category: Illes K]] |
| - | [[Category: Nagar, B]] | + | [[Category: Nagar B]] |
| - | [[Category: Gdsl esterase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Lipopolysaccharide]]
| + | |
| - | [[Category: Lp]]
| + | |
| - | [[Category: Saposin]]
| + | |
| Structural highlights
Function
AOAH_HUMAN Removes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (PubMed:1883828, PubMed:8089145). By breaking down LPS, terminates the host response to bacterial infection and prevents prolonged and damaging inflammatory responses (By similarity). In peritoneal macrophages, seems to be important for recovery from a state of immune tolerance following infection by Gram-negative bacteria (By similarity).[UniProtKB:O35298][1] [2]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hagen FS, Grant FJ, Kuijper JL, Slaughter CA, Moomaw CR, Orth K, O'Hara PJ, Munford RS. Expression and characterization of recombinant human acyloxyacyl hydrolase, a leukocyte enzyme that deacylates bacterial lipopolysaccharides. Biochemistry. 1991 Aug 27;30(34):8415-23. PMID:1883828
- ↑ Staab JF, Ginkel DL, Rosenberg GB, Munford RS. A saposin-like domain influences the intracellular localization, stability, and catalytic activity of human acyloxyacyl hydrolase. J Biol Chem. 1994 Sep 23;269(38):23736-42. PMID:8089145
- ↑ 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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