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==Crystal Structure of the PSEUDOMONAS AERUGINOSA LpxC/LPC-009 complex== | |||
<StructureSection load='3p3e' size='340' side='right' caption='[[3p3e]], [[Resolution|resolution]] 1.28Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3p3e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P3E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P3E FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3P3:N-[(1S,2R)-2-HYDROXY-1-(HYDROXYCARBAMOYL)PROPYL]-4-(4-PHENYLBUTA-1,3-DIYN-1-YL)BENZAMIDE'>3P3</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ves|2ves]], [[3p3c|3p3c]], [[3p3g|3p3g]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">envA, lpxC, PA4406 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 Pseudomonas aeruginosa])</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=3p3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p3e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3p3e RCSB], [http://www.ebi.ac.uk/pdbsum/3p3e PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
LpxC is an essential enzyme in the lipid A biosynthetic pathway in gram-negative bacteria. Several promising antimicrobial lead compounds targeting LpxC have been reported, though they typically display a large variation in potency against different gram-negative pathogens. We report that inhibitors with a diacetylene scaffold effectively overcome the resistance caused by sequence variation in the LpxC substrate-binding passage. Compound binding is captured in complex with representative LpxC orthologs, and structural analysis reveals large conformational differences that mostly reflect inherent molecular features of distinct LpxC orthologs, whereas ligand-induced structural adaptations occur at a smaller scale. These observations highlight the need for a molecular understanding of inherent structural features and conformational plasticity of LpxC enzymes for optimizing LpxC inhibitors as broad-spectrum antibiotics against gram-negative infections. | |||
Species-Specific and Inhibitor-Dependent Conformations of LpxC: Implications for Antibiotic Design.,Lee CJ, Liang X, Chen X, Zeng D, Joo SH, Chung HS, Barb AW, Swanson SM, Nicholas RA, Li Y, Toone EJ, Raetz CR, Zhou P Chem Biol. 2010 Dec 16. PMID:21167751<ref>PMID:21167751</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== | ==See Also== | ||
*[[UDP-3-O-acyl-N-acetylglucosamine deacetylase|UDP-3-O-acyl-N-acetylglucosamine deacetylase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Pseudomonas aeruginosa]] | [[Category: Pseudomonas aeruginosa]] | ||
[[Category: Lee, C J]] | [[Category: Lee, C J]] | ||
[[Category: Zhou, P | [[Category: Zhou, P]] | ||
[[Category: Acyl udp-glcnac]] | [[Category: Acyl udp-glcnac]] | ||
[[Category: Antibiotic]] | [[Category: Antibiotic]] | ||
Revision as of 09:51, 19 December 2014
Crystal Structure of the PSEUDOMONAS AERUGINOSA LpxC/LPC-009 complexCrystal Structure of the PSEUDOMONAS AERUGINOSA LpxC/LPC-009 complex
Structural highlights
Publication Abstract from PubMedLpxC is an essential enzyme in the lipid A biosynthetic pathway in gram-negative bacteria. Several promising antimicrobial lead compounds targeting LpxC have been reported, though they typically display a large variation in potency against different gram-negative pathogens. We report that inhibitors with a diacetylene scaffold effectively overcome the resistance caused by sequence variation in the LpxC substrate-binding passage. Compound binding is captured in complex with representative LpxC orthologs, and structural analysis reveals large conformational differences that mostly reflect inherent molecular features of distinct LpxC orthologs, whereas ligand-induced structural adaptations occur at a smaller scale. These observations highlight the need for a molecular understanding of inherent structural features and conformational plasticity of LpxC enzymes for optimizing LpxC inhibitors as broad-spectrum antibiotics against gram-negative infections. Species-Specific and Inhibitor-Dependent Conformations of LpxC: Implications for Antibiotic Design.,Lee CJ, Liang X, Chen X, Zeng D, Joo SH, Chung HS, Barb AW, Swanson SM, Nicholas RA, Li Y, Toone EJ, Raetz CR, Zhou P Chem Biol. 2010 Dec 16. PMID:21167751[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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