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| | ==Crystal structure of the outer membrane enzyme PagL== | | ==Crystal structure of the outer membrane enzyme PagL== |
| - | <StructureSection load='2erv' size='340' side='right' caption='[[2erv]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='2erv' size='340' side='right'caption='[[2erv]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2erv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ERV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ERV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2erv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ERV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ERV 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=CXE:PENTAETHYLENE+GLYCOL+MONODECYL+ETHER'>CXE</scene></td></tr> | + | </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=CXE:PENTAETHYLENE+GLYCOL+MONODECYL+ETHER'>CXE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PA4661 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 "Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PA4661 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 "Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885])</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=2erv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2erv OCA], [http://pdbe.org/2erv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2erv RCSB], [http://www.ebi.ac.uk/pdbsum/2erv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2erv ProSAT]</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=2erv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2erv OCA], [https://pdbe.org/2erv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2erv RCSB], [https://www.ebi.ac.uk/pdbsum/2erv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2erv ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PAGL_PSEAE PAGL_PSEAE]] Has lipid A 3-O-deacylase activity. Hydrolyzes the ester bond at the 3 position of lipid A, a bioactive component of lipopolysaccharide (LPS), thereby releasing the primary fatty acyl moiety. Lacks fatty acyl chain-length specificity as removes both 3-OH C10 and 3-OH C14 fatty acids from lipid A.<ref>PMID:15611102</ref> <ref>PMID:16352835</ref> <ref>PMID:16632613</ref> | + | [[https://www.uniprot.org/uniprot/PAGL_PSEAE PAGL_PSEAE]] Has lipid A 3-O-deacylase activity. Hydrolyzes the ester bond at the 3 position of lipid A, a bioactive component of lipopolysaccharide (LPS), thereby releasing the primary fatty acyl moiety. Lacks fatty acyl chain-length specificity as removes both 3-OH C10 and 3-OH C14 fatty acids from lipid A.<ref>PMID:15611102</ref> <ref>PMID:16352835</ref> <ref>PMID:16632613</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/er/2erv_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/er/2erv_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Bonvin, A M]] | | [[Category: Bonvin, A M]] |
| | [[Category: Egmond, M R]] | | [[Category: Egmond, M R]] |
| Structural highlights
Function
[PAGL_PSEAE] Has lipid A 3-O-deacylase activity. Hydrolyzes the ester bond at the 3 position of lipid A, a bioactive component of lipopolysaccharide (LPS), thereby releasing the primary fatty acyl moiety. Lacks fatty acyl chain-length specificity as removes both 3-OH C10 and 3-OH C14 fatty acids from lipid A.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Pathogenic gram-negative bacteria can modify the lipid A portion of their lipopolysaccharide in response to environmental stimuli. 3-O-deacylation of lipid A by the outer membrane enzyme PagL modulates signaling through Toll-like receptor 4, leading to a reduced host immune response. We found that PagL is widely disseminated among gram-negative bacteria. Only four residues are conserved: a Ser, His, Phe, and Asn residue. Here, we describe the crystal structure of PagL from Pseudomonas aeruginosa to 2.0-A resolution. It consists of an eight-stranded beta-barrel with the axis tilted by approximately 30 degrees with respect to the lipid bilayer. The structure reveals that PagL contains an active site with a Ser-His-Glu catalytic triad and an oxyanion hole that comprises the conserved Asn. The importance of active site residues was confirmed in mutagenesis studies. Although PagL is most likely active as a monomer, its active site architecture shows high resemblance to that of the dimeric 12-stranded outer membrane phospholipase A. Modeling of the substrate lipid X onto the active site reveals that the 3-O-acyl chain is accommodated in a hydrophobic groove perpendicular to the membrane plane. In addition, an aspartate makes a hydrogen bond with the hydroxyl group of the 3-O-acyl chain, probably providing specificity of PagL toward lipid A.
Crystal structure and catalytic mechanism of the LPS 3-O-deacylase PagL from Pseudomonas aeruginosa.,Rutten L, Geurtsen J, Lambert W, Smolenaers JJ, Bonvin AM, de Haan A, van der Ley P, Egmond MR, Gros P, Tommassen J Proc Natl Acad Sci U S A. 2006 May 2;103(18):7071-6. Epub 2006 Apr 21. PMID:16632613[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Geurtsen J, Steeghs L, Hove JT, van der Ley P, Tommassen J. Dissemination of lipid A deacylases (pagL) among gram-negative bacteria: identification of active-site histidine and serine residues. J Biol Chem. 2005 Mar 4;280(9):8248-59. Epub 2004 Dec 20. PMID:15611102 doi:http://dx.doi.org/10.1074/jbc.M414235200
- ↑ Ernst RK, Adams KN, Moskowitz SM, Kraig GM, Kawasaki K, Stead CM, Trent MS, Miller SI. The Pseudomonas aeruginosa lipid A deacylase: selection for expression and loss within the cystic fibrosis airway. J Bacteriol. 2006 Jan;188(1):191-201. PMID:16352835 doi:http://dx.doi.org/10.1128/JB.188.1.191-201.2006
- ↑ Rutten L, Geurtsen J, Lambert W, Smolenaers JJ, Bonvin AM, de Haan A, van der Ley P, Egmond MR, Gros P, Tommassen J. Crystal structure and catalytic mechanism of the LPS 3-O-deacylase PagL from Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 2006 May 2;103(18):7071-6. Epub 2006 Apr 21. PMID:16632613
- ↑ Rutten L, Geurtsen J, Lambert W, Smolenaers JJ, Bonvin AM, de Haan A, van der Ley P, Egmond MR, Gros P, Tommassen J. Crystal structure and catalytic mechanism of the LPS 3-O-deacylase PagL from Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 2006 May 2;103(18):7071-6. Epub 2006 Apr 21. PMID:16632613
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