5u39: Difference between revisions
New page: '''Unreleased structure''' The entry 5u39 is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Pseudomonas aeruginosa LpxC in complex with CHIR-090== | |||
<StructureSection load='5u39' size='340' side='right'caption='[[5u39]], [[Resolution|resolution]] 1.75Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5u39]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U39 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U39 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]] 1.75Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C90:N-{(1S,2R)-2-HYDROXY-1-[(HYDROXYAMINO)CARBONYL]PROPYL}-4-{[4-(MORPHOLIN-4-YLMETHYL)PHENYL]ETHYNYL}BENZAMIDE'>C90</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5u39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u39 OCA], [https://pdbe.org/5u39 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u39 RCSB], [https://www.ebi.ac.uk/pdbsum/5u39 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u39 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/LPXC_PSEAE LPXC_PSEAE] 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;"> | |||
== Publication Abstract from PubMed == | |||
Over the past several decades, the frequency of antibacterial resistance in hospitals, including multidrug resistance (MDR) and its association with serious infectious diseases, has increased at alarming rates. Pseudomonas aeruginosa is a leading cause of nosocomial infections, and resistance to virtually all approved antibacterial agents is emerging in this pathogen. To address the need for new agents to treat MDR P. aeruginosa, we focused on inhibiting the first committed step in the biosynthesis of lipid A, the deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by the enzyme LpxC. We approached this through the design, synthesis, and biological evaluation of novel hydroxamic acid LpxC inhibitors, exemplified by 1, where cytotoxicity against mammalian cell lines was reduced, solubility and plasma-protein binding were improved while retaining potent anti-pseudomonal activity in vitro and in vivo. | |||
Design, Synthesis, and Properties of a Potent Inhibitor of Pseudomonas aeruginosa Deacetylase LpxC.,Piizzi G, Parker DT, Peng Y, Dobler M, Patnaik A, Wattanasin S, Liu E, Lenoir F, Nunez J, Kerrigan J, McKenney D, Osborne C, Yu D, Lanieri L, Bojkovic J, Dzink-Fox J, Lilly MD, Sprague ER, Lu Y, Wang H, Ranjitkar S, Xie L, Wang B, Glick M, Hamann LG, Tommasi R, Yang X, Dean CR J Med Chem. 2017 Jun 22;60(12):5002-5014. doi: 10.1021/acs.jmedchem.7b00377. Epub, 2017 Jun 9. PMID:28549219<ref>PMID:28549219</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5u39" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[UDP-3-O-acyl-N-acetylglucosamine deacetylase|UDP-3-O-acyl-N-acetylglucosamine deacetylase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Pseudomonas aeruginosa PAO1]] | |||
[[Category: Sprague ER]] | |||
Latest revision as of 16:19, 4 October 2023
Pseudomonas aeruginosa LpxC in complex with CHIR-090Pseudomonas aeruginosa LpxC in complex with CHIR-090
Structural highlights
FunctionLPXC_PSEAE Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell. Publication Abstract from PubMedOver the past several decades, the frequency of antibacterial resistance in hospitals, including multidrug resistance (MDR) and its association with serious infectious diseases, has increased at alarming rates. Pseudomonas aeruginosa is a leading cause of nosocomial infections, and resistance to virtually all approved antibacterial agents is emerging in this pathogen. To address the need for new agents to treat MDR P. aeruginosa, we focused on inhibiting the first committed step in the biosynthesis of lipid A, the deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by the enzyme LpxC. We approached this through the design, synthesis, and biological evaluation of novel hydroxamic acid LpxC inhibitors, exemplified by 1, where cytotoxicity against mammalian cell lines was reduced, solubility and plasma-protein binding were improved while retaining potent anti-pseudomonal activity in vitro and in vivo. Design, Synthesis, and Properties of a Potent Inhibitor of Pseudomonas aeruginosa Deacetylase LpxC.,Piizzi G, Parker DT, Peng Y, Dobler M, Patnaik A, Wattanasin S, Liu E, Lenoir F, Nunez J, Kerrigan J, McKenney D, Osborne C, Yu D, Lanieri L, Bojkovic J, Dzink-Fox J, Lilly MD, Sprague ER, Lu Y, Wang H, Ranjitkar S, Xie L, Wang B, Glick M, Hamann LG, Tommasi R, Yang X, Dean CR J Med Chem. 2017 Jun 22;60(12):5002-5014. doi: 10.1021/acs.jmedchem.7b00377. Epub, 2017 Jun 9. PMID:28549219[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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