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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. 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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.81Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5dep|5dep]]</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='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'>[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='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]</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;">
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| - | == Publication Abstract from PubMed ==
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| - | 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.
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| - | 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<ref>PMID:26352800</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | ==See Also== |
| - | </div>
| + | *[[UDP-N-acetylglucosamine acyltransferase|UDP-N-acetylglucosamine acyltransferase]] |
| - | <div class="pdbe-citations 5dem" style="background-color:#fffaf0;"></div>
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| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Chen, Y]] | + | [[Category: Large Structures]] |
| - | [[Category: Smith, E W]] | + | [[Category: Pseudomonas aeruginosa PA7]] |
| - | [[Category: Acyltransferase catalytic domain]] | + | [[Category: Chen Y]] |
| - | [[Category: Fatty acid]] | + | [[Category: Smith EW]] |
| - | [[Category: Hydrocarbon ruler]]
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| - | [[Category: Lipid some]]
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| - | [[Category: Substrate specificity]]
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| - | [[Category: Transferase]]
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| - | [[Category: Uridine diphosphate n-acetylglucosamine]]
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