2jf3: Difference between revisions
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== | ==Nucleotide substrate binding by UDP-N-acetylglucosamine acyltransferase== | ||
[[http://www.uniprot.org/uniprot/LPXA_ECOLI LPXA_ECOLI | <StructureSection load='2jf3' size='340' side='right'caption='[[2jf3]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2jf3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JF3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JF3 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]] 3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UD1:URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE'>UD1</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=2jf3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jf3 OCA], [https://pdbe.org/2jf3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jf3 RCSB], [https://www.ebi.ac.uk/pdbsum/2jf3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jf3 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/jf/2jf3_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=2jf3 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Lipid A is an integral component of the lipopolysaccharide (LPS) that forms the selective and protective outer monolayer of Gram-negative bacteria, and is essential for bacterial growth and viability. UDP-N-acetylglucosamine acyltransferase (LpxA) initiates lipid A biosynthesis by catalyzing the transfer of R-3-hydroxymyristic acid from acyl carrier protein to the 3'-hydroxyl group of UDP-GlcNAc. The enzyme is a homotrimer, and previous studies suggested that the active site lies within a positively charged cleft formed at the subunit-subunit interface. The crystal structure of Escherichia coli LpxA in complex with UDP-GlcNAc reveals details of the substrate-binding site, with prominent hydrophilic interactions between highly conserved clusters of residues (Asn198, Glu200, Arg204 and Arg205) with UDP, and (Asp74, His125, His144 and Gln161) with the GlcNAc moiety. These interactions serve to bind and orient the substrate for catalysis. The crystallographic model supports previous results, which suggest that acylation occurs via nucleophilic attack of deprotonated UDP-GlcNAc on the acyl donor in a general base-catalyzed mechanism involving a catalytic dyad of His125 and Asp126. His125, the general base, interacts with the 3'-hydroxyl group of UDP-GlcNAc to generate the nucleophile. The Asp126 side-chain accepts a hydrogen bond from His125 and helps orient the general base to participate in catalysis. Comparisons with an LpxA:peptide inhibitor complex indicate that the peptide competes with both nucleotide and acyl carrier protein substrates. | |||
Nucleotide substrate recognition by UDP-N-acetylglucosamine acyltransferase (LpxA) in the first step of lipid A biosynthesis.,Ulaganathan V, Buetow L, Hunter WN J Mol Biol. 2007 Jun 1;369(2):305-12. Epub 2007 Mar 21. PMID:17434525<ref>PMID:17434525</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
< | </div> | ||
<div class="pdbe-citations 2jf3" style="background-color:#fffaf0;"></div> | |||
[[ | ==See Also== | ||
[[Category: | *[[UDP-N-acetylglucosamine acyltransferase|UDP-N-acetylglucosamine acyltransferase]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Escherichia coli]] | |||
[[Category: Large Structures]] | |||
[[Category: Buetow L]] | |||
[[Category: Hunter WN]] | |||
[[Category: Ulaganathan V]] | |||
Latest revision as of 17:45, 13 December 2023
Nucleotide substrate binding by UDP-N-acetylglucosamine acyltransferaseNucleotide substrate binding by UDP-N-acetylglucosamine acyltransferase
Structural highlights
FunctionLPXA_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 Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedLipid A is an integral component of the lipopolysaccharide (LPS) that forms the selective and protective outer monolayer of Gram-negative bacteria, and is essential for bacterial growth and viability. UDP-N-acetylglucosamine acyltransferase (LpxA) initiates lipid A biosynthesis by catalyzing the transfer of R-3-hydroxymyristic acid from acyl carrier protein to the 3'-hydroxyl group of UDP-GlcNAc. The enzyme is a homotrimer, and previous studies suggested that the active site lies within a positively charged cleft formed at the subunit-subunit interface. The crystal structure of Escherichia coli LpxA in complex with UDP-GlcNAc reveals details of the substrate-binding site, with prominent hydrophilic interactions between highly conserved clusters of residues (Asn198, Glu200, Arg204 and Arg205) with UDP, and (Asp74, His125, His144 and Gln161) with the GlcNAc moiety. These interactions serve to bind and orient the substrate for catalysis. The crystallographic model supports previous results, which suggest that acylation occurs via nucleophilic attack of deprotonated UDP-GlcNAc on the acyl donor in a general base-catalyzed mechanism involving a catalytic dyad of His125 and Asp126. His125, the general base, interacts with the 3'-hydroxyl group of UDP-GlcNAc to generate the nucleophile. The Asp126 side-chain accepts a hydrogen bond from His125 and helps orient the general base to participate in catalysis. Comparisons with an LpxA:peptide inhibitor complex indicate that the peptide competes with both nucleotide and acyl carrier protein substrates. Nucleotide substrate recognition by UDP-N-acetylglucosamine acyltransferase (LpxA) in the first step of lipid A biosynthesis.,Ulaganathan V, Buetow L, Hunter WN J Mol Biol. 2007 Jun 1;369(2):305-12. Epub 2007 Mar 21. PMID:17434525[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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