9eng: Difference between revisions

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-'''Unreleased structure'''
-The entry 9eng is ON HOLD  until Paper Publication
+==Structure of K.pneumoniae LpxH in complex with EBL-3218==
+<StructureSection load='9eng' size='340' side='right'caption='[[9eng]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9eng]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9ENG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9ENG 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]] 2.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1H55:~{N}-[4-[4-[3,5-bis(chloranyl)phenyl]piperazin-1-yl]sulfonylphenyl]-3-(methylsulfonylamino)benzamide'>A1H55</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=9eng FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9eng OCA], [https://pdbe.org/9eng PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9eng RCSB], [https://www.ebi.ac.uk/pdbsum/9eng PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9eng ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/LPXH_KLEP7 LPXH_KLEP7] Hydrolyzes the pyrophosphate bond of UDP-2,3-diacylglucosamine to yield 2,3-diacylglucosamine 1-phosphate (lipid X) and UMP by catalyzing the attack of water at the alpha-P atom. Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell.[HAMAP-Rule:MF_00575]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+New antibacterial compounds are urgently needed, especially for infections caused by the top-priority Gram-negative bacteria that are increasingly difficult to treat. Lipid A is a key component of the Gram-negative outer membrane and the LpxH enzyme plays an important role in its biosynthesis, making it a promising antibacterial target. Inspired by previously reported ortho-N-methyl-sulfonamidobenzamide-based LpxH inhibitors, novel benzamide substitutions were explored in this work to assess their in vitro activity. Our findings reveal that maintaining wild-type antibacterial activity necessitates removal of the N-methyl group when shifting the ortho-N-methyl-sulfonamide to the meta-position. This discovery led to the synthesis of meta-sulfonamidobenzamide analogs with potent antibacterial activity and enzyme inhibition. Moreover, we demonstrate that modifying the benzamide scaffold can alter blocking of the cardiac voltage-gated potassium ion channel hERG. Furthermore, two LpxH-bound X-ray structures show how the enzyme-ligand interactions of the meta-sulfonamidobenzamide analogs differ from those of the previously reported ortho analogs. Overall, our study has identified meta-sulfonamidobenzamide derivatives as promising LpxH inhibitors with the potential for optimization in future antibacterial hit-to-lead programs.
-Authors:
+Design, synthesis, and in vitro biological evaluation of meta-sulfonamidobenzamide-based antibacterial LpxH inhibitors.,Benediktsdottir A, Sooriyaarachchi S, Cao S, Ottosson NE, Lindstrom S, Lundgren B, Kloditz K, Lola D, Bobileva O, Loza E, Hughes D, Jones TA, Mowbray SL, Zamaratski E, Sandstrom A, Karlen A Eur J Med Chem. 2024 Nov 15;278:116790. doi: 10.1016/j.ejmech.2024.116790. Epub , 2024 Aug 22. PMID:39236497<ref>PMID:39236497</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9eng" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Klebsiella pneumoniae]]
+[[Category: Large Structures]]
+[[Category: Bergfors T]]
+[[Category: Jones TA]]
+[[Category: Mowbray SL]]
+[[Category: Sooriyaarachchi S]]