2aq9
From Proteopedia
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| - | [[Image:2aq9.gif|left|200px]] | ||
| - | + | ==Structure of E. coli LpxA with a bound peptide that is competitive with acyl-ACP== | |
| - | + | <StructureSection load='2aq9' size='340' side='right'caption='[[2aq9]], [[Resolution|resolution]] 1.80Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | | | + | <table><tr><td colspan='2'>[[2aq9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AQ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AQ9 FirstGlance]. <br> |
| - | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> | |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=2aq9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aq9 OCA], [https://pdbe.org/2aq9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aq9 RCSB], [https://www.ebi.ac.uk/pdbsum/2aq9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aq9 ProSAT]</span></td></tr> | |
| - | + | </table> | |
| - | + | == Function == | |
| - | + | [https://www.uniprot.org/uniprot/LPXA_ECOLI LPXA_ECOLI] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell.[HAMAP-Rule:MF_00387] | |
| - | + | == Evolutionary Conservation == | |
| - | == | + | [[Image:Consurf_key_small.gif|200px|right]] |
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/aq/2aq9_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2aq9 ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
UDP-GlcNAc acyltransferase (LpxA) catalyzes the first step of lipid A biosynthesis, the transfer of the R-3-hydroxyacyl chain from R-3-hydroxyacyl acyl carrier protein (ACP) to the glucosamine 3-OH group of UDP-GlcNAc. LpxA is essential for the growth of Escherichia coli and related Gram-negative bacteria. The crystal structure of the E. coli LpxA homotrimer, determined previously at 2.6 A in the absence of substrates or inhibitors, revealed that LpxA contains an unusual, left-handed parallel beta-helix fold. We now present the crystal structure at 1.8 A resolution of E. coli LpxA in a complex with a pentadecapeptide, peptide 920. Three peptides, each of which adopts a beta-hairpin conformation, are bound per LpxA trimer. The peptides are located at the interfaces of adjacent subunits in the vicinity of the three active sites. Each peptide interacts with residues from both adjacent subunits. Peptide 920 is a potent inhibitor of E. coli LpxA (Ki = 50 nM). It is competitive with respect to acyl-ACP but not UDP-GlcNAc. The compact beta-turn structure of peptide 920 bound to LpxA may open previously uncharacterized approaches to the rational design of LpxA inhibitors with antibiotic activity. | UDP-GlcNAc acyltransferase (LpxA) catalyzes the first step of lipid A biosynthesis, the transfer of the R-3-hydroxyacyl chain from R-3-hydroxyacyl acyl carrier protein (ACP) to the glucosamine 3-OH group of UDP-GlcNAc. LpxA is essential for the growth of Escherichia coli and related Gram-negative bacteria. The crystal structure of the E. coli LpxA homotrimer, determined previously at 2.6 A in the absence of substrates or inhibitors, revealed that LpxA contains an unusual, left-handed parallel beta-helix fold. We now present the crystal structure at 1.8 A resolution of E. coli LpxA in a complex with a pentadecapeptide, peptide 920. Three peptides, each of which adopts a beta-hairpin conformation, are bound per LpxA trimer. The peptides are located at the interfaces of adjacent subunits in the vicinity of the three active sites. Each peptide interacts with residues from both adjacent subunits. Peptide 920 is a potent inhibitor of E. coli LpxA (Ki = 50 nM). It is competitive with respect to acyl-ACP but not UDP-GlcNAc. The compact beta-turn structure of peptide 920 bound to LpxA may open previously uncharacterized approaches to the rational design of LpxA inhibitors with antibiotic activity. | ||
| - | + | Structure of UDP-N-acetylglucosamine acyltransferase with a bound antibacterial pentadecapeptide.,Williams AH, Immormino RM, Gewirth DT, Raetz CR Proc Natl Acad Sci U S A. 2006 Jul 18;103(29):10877-82. Epub 2006 Jul 11. PMID:16835299<ref>PMID:16835299</ref> | |
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| - | Structure of UDP-N-acetylglucosamine acyltransferase with a bound antibacterial pentadecapeptide., Williams AH, Immormino RM, Gewirth DT, Raetz CR | + | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 2aq9" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Escherichia coli K-12]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Gewirth DT]] | ||
| + | [[Category: Immormino RM]] | ||
| + | [[Category: Raetz CR]] | ||
| + | [[Category: Williams AH]] | ||
Current revision
Structure of E. coli LpxA with a bound peptide that is competitive with acyl-ACP
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