4u3d: Difference between revisions
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<StructureSection load='4u3d' size='340' side='right'caption='[[4u3d]], [[Resolution|resolution]] 1.25Å' scene=''> | <StructureSection load='4u3d' size='340' side='right'caption='[[4u3d]], [[Resolution|resolution]] 1.25Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4u3d]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4u3d]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aquifex_aeolicus_VF5 Aquifex aeolicus VF5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U3D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U3D FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3BX:N-HYDROXY-4-[(4-{[4-(MORPHOLIN-4-YLMETHYL)PHENYL]ETHYNYL}PHENOXY)METHYL]TETRAHYDRO-2H-PYRAN-4-CARBOXAMIDE'>3BX</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3BX:N-HYDROXY-4-[(4-{[4-(MORPHOLIN-4-YLMETHYL)PHENYL]ETHYNYL}PHENOXY)METHYL]TETRAHYDRO-2H-PYRAN-4-CARBOXAMIDE'>3BX</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</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=4u3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u3d OCA], [https://pdbe.org/4u3d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u3d RCSB], [https://www.ebi.ac.uk/pdbsum/4u3d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u3d ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/LPXC_AQUAE LPXC_AQUAE] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell (By similarity). | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Aquifex aeolicus VF5]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Olivier | [[Category: Olivier NB]] | ||
Revision as of 10:59, 22 March 2023
LpxC from A.Aaeolicus in complex with 4-[[4-[2-[4-(morpholinomethyl)phenyl]ethynyl]phenoxy]methyl]tetrahydropyran-4-carbohydroxamic acid (compound 9)
Structural highlights
FunctionLPXC_AQUAE Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell (By similarity). Publication Abstract from PubMedIn the search for novel Gram-negative agents, we performed a comprehensive search of the AstraZeneca collection and identified a tetrahydropyran-based matrix metalloprotease (MMP) inhibitor that demonstrated nanomolar inhibition of UDP-3-O-(acyl)-N-acetylglucosamine deacetylase (LpxC). Crystallographic studies in Aquifex aeolicus LpxC indicated the tetrahydropyran engaged in the same hydrogen bonds and van der Waals interactions as other known inhibitors. Systematic optimization of three locales on the scaffold provided compounds with improved Gram-negative activity. However, the optimization of LpxC activity was not accompanied by reduced inhibition of MMPs. Comparison of the crystal structure of the native product, UDP-3-O-(acyl)-glucosamine, in Aquifex aeolicus to the structure of a tetrahydropyran-based inhibitor indicates pathways for future optimization. Synthesis, Structure, and SAR of Tetrahydropyran-Based LpxC Inhibitors.,Murphy-Benenato KE, Olivier N, Choy A, Ross PL, Miller MD, Thresher J, Gao N, Hale MR ACS Med Chem Lett. 2014 Sep 23;5(11):1213-1218. eCollection 2014 Nov 13. PMID:25408833[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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