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| | ==Structure of Pseudomonas aeruginosa LpxA== | | ==Structure of Pseudomonas aeruginosa LpxA== |
| - | <StructureSection load='5dem' size='340' side='right' caption='[[5dem]], [[Resolution|resolution]] 1.81Å' scene=''> | + | <StructureSection load='5dem' size='340' side='right'caption='[[5dem]], [[Resolution|resolution]] 1.81Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5dem]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Psea7 Psea7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DEM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DEM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5dem]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PA7 Pseudomonas aeruginosa PA7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DEM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DEM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5dep|5dep]]</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=5dem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dem OCA], [https://pdbe.org/5dem PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dem RCSB], [https://www.ebi.ac.uk/pdbsum/5dem PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dem ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lpxA, PSPA7_1495 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=381754 PSEA7])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine_O-acyltransferase Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.129 2.3.1.129] </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=5dem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dem OCA], [http://pdbe.org/5dem PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dem RCSB], [http://www.ebi.ac.uk/pdbsum/5dem PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dem ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LPXA_PSEA7 LPXA_PSEA7]] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell. | + | [https://www.uniprot.org/uniprot/LPXA_PSEA7 LPXA_PSEA7] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5dem" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5dem" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[UDP-N-acetylglucosamine acyltransferase|UDP-N-acetylglucosamine acyltransferase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Psea7]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, Y]] | + | [[Category: Pseudomonas aeruginosa PA7]] |
| - | [[Category: Smith, E W]] | + | [[Category: Chen Y]] |
| - | [[Category: Acyltransferase catalytic domain]] | + | [[Category: Smith EW]] |
| - | [[Category: Fatty acid]]
| + | |
| - | [[Category: Hydrocarbon ruler]]
| + | |
| - | [[Category: Lipid some]]
| + | |
| - | [[Category: Substrate specificity]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Uridine diphosphate n-acetylglucosamine]]
| + | |
| Structural highlights
Function
LPXA_PSEA7 Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell.
Publication Abstract from PubMed
In Gram-negative bacteria, the first step of lipid A biosynthesis is catalyzed by UDP-N-acetylglucosamine acyltransferase (LpxA) through the transfer of a R-3-hydroxyacyl chain from the acyl carrier protein (ACP) to the 3-hydroxyl group of UDP-GlcNAc. Previous studies suggest that LpxA is a critical determinant of the acyl chain length found in lipid A, which varies among species of bacteria. In Escherichia coli and Leptospira interrogans, LpxA prefers to incorporate longer R-3-hydroxyacyl chains (C14 and C12, respectively), whereas in Pseudomonas aeruginosa, the enzyme is selective for R-3-hydroxydecanoyl, a 10-hydrocarbon long acyl chain. We now report three P. aeruginosa LpxA crystal structures: apo protein, substrate complex with UDP-GlcNAc, and product complex with UDP-3-O-(R-3-hydroxydecanoyl)-GlcNAc. A comparison between the apo form and complexes identifies key residues that position UDP-GlcNAc appropriately for catalysis and supports the role of catalytic His121 in activating the UDP-GlcNAc 3-hydroxyl group for nucleophilic attack during the reaction. The product-complex structure, for the first time, offers structural insights into how Met169 serves to constrain the length of the acyl chain and thus functions as the so-called hydrocarbon ruler. Furthermore, compared with ortholog LpxA structures, the purported oxyanion hole, formed by the backbone amide group of Gly139, displays a different conformation in P. aeruginosa LpxA, which suggests flexibility of this structural feature important for catalysis and the potential need for substrate-induced conformational change in catalysis. Taken together, the three structures provide valuable insights into P. aeruginosa LpxA catalysis and substrate specificity as well as templates for future inhibitor discovery.
Structures of Pseudomonas aeruginosa LpxA Reveal the Basis for Its Substrate Selectivity.,Smith EW, Zhang X, Behzadi C, Andrews LD, Cohen F, Chen Y Biochemistry. 2015 Sep 29;54(38):5937-48. doi: 10.1021/acs.biochem.5b00720. Epub , 2015 Sep 18. PMID:26352800[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Smith EW, Zhang X, Behzadi C, Andrews LD, Cohen F, Chen Y. Structures of Pseudomonas aeruginosa LpxA Reveal the Basis for Its Substrate Selectivity. Biochemistry. 2015 Sep 29;54(38):5937-48. doi: 10.1021/acs.biochem.5b00720. Epub , 2015 Sep 18. PMID:26352800 doi:http://dx.doi.org/10.1021/acs.biochem.5b00720
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