4u3d
From Proteopedia
(Difference between revisions)
| (6 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| + | |||
==LpxC from A.Aaeolicus in complex with 4-[[4-[2-[4-(morpholinomethyl)phenyl]ethynyl]phenoxy]methyl]tetrahydropyran-4-carbohydroxamic acid (compound 9)== | ==LpxC from A.Aaeolicus in complex with 4-[[4-[2-[4-(morpholinomethyl)phenyl]ethynyl]phenoxy]methyl]tetrahydropyran-4-carbohydroxamic acid (compound 9)== | ||
| - | <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. 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 [ | + | <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><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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.25Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <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> |
| - | <table> | + | <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> |
| + | </table> | ||
| + | == 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;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | In 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<ref>PMID:25408833</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4u3d" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[UDP-3-O-acyl-N-acetylglucosamine deacetylase|UDP-3-O-acyl-N-acetylglucosamine deacetylase]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Aquifex aeolicus VF5]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Olivier NB]] |
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
Current revision
LpxC from A.Aaeolicus in complex with 4-[[4-[2-[4-(morpholinomethyl)phenyl]ethynyl]phenoxy]methyl]tetrahydropyran-4-carbohydroxamic acid (compound 9)
| |||||||||||
